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Highlights • β-caseins from human milk and from donkey, goat, and sheep milk have been purified. • Similar self-assembling behaviour between β-casein from different species was found. • Lower hypoallergenic potential of donkey and human β-caseins was determined. • Possible use of β-casein from other milk sources as nanocarriers has been suggested. Graphical abstract Abstract Caseins are a family of proteins constituted by α-caseins (αs-1 and αs-2 caseins), β-caseins and κ-caseins. β-caseins, in particular, show a temperature and concentration-dependent self-assembling behaviour. Recently, β-casein micelles have been proposed as natural nanocarriers for the delivery of hydrophobic compounds, promoting their bioavailability. Until now, all studies regarding both chemical-physical characterization and applications of β-caseins have employed the protein of bovine origin. However, it could be interesting to exploit the use of β-caseins from other milk sources for their potential encapsulation ability and immunogenicity but, at present, no information on the self-assembling behaviour is available for β-caseins from the milk of species different from bovine. In this work, for the first time, β-caseins from human milk and from donkey, goat, and sheep milk were purified and their self-assembling behaviour was compared to that of a commercial bovine β-casein, the only one for which the concentration and temperature aggregation behaviour is known. Furthermore, a preliminary evaluation of the immunogenicity potential of β-casein from other milk sources has been performed by cross-reaction experiments using anti-β-casein antibodies from bovine origin. The results indicated a similar self-assembling profile among all β-caseins examined compared to the bovine β-casein, suggesting the possible use of β-casein from other milk sources as nanocarriers. Since donkey and human β-casein do not cross-react with bovine anti-β-casein antibodies, they could be particularly interesting for the development of self-assembling systems with lower hypoallergenic potential. [ABSTRACT FROM AUTHOR]

Acoustics is one of the emerging technologies developed to minimize processing, maximize quality and ensure the safety of pharmaceutical, food and chemical products. The operating principle of acoustic spectroscopy is the measurement of the ultrasound pulse intensity and phase after its propagation through a sample. The main goal of this technique is to characterise concentrated colloidal dispersions without dilution, in such a way as to be able to analyse non-transparent and even highly structured systems. This review presents the state of the art of ultrasound-based techniques in pharmaceutical pre-formulation and formulation steps, showing their potential, applicability and limits. It reports in a simplified version the theory behind acoustic spectroscopy, describes the most common equipment on the market, and finally overviews different studies performed on systems and materials used in the pharmaceutical or related fields. [ABSTRACT FROM AUTHOR]

Dextrans are a class of carbohydrate polymers extensively applied in pharmaceutical applications, particularly as drug conjugate macromolecular carriers or drug delivery systems. These polysaccharides improve the stability of the therapeutics enabling also the control of their release, via either the parenteral and or oral routes. In the latter case, due to their gel forming ability they may have potential as hydrophilic matrix tablets for sustained drug release. In this paper, we investigated the behaviour of different molecular weight (1, 40, 500 and 2300 kDa) dextrans as tabletting excipients. Powder particle size and hygroscopic studies have been reported, together with tabletability, tablet stability and tablet swelling. Moreover we use tramadol as model compound to evaluate the ability of dextrans to control drug dissolution. The results suggest that dextrans with lower molecular weights may be a promising excipient to be used as filler for immediate release tablets, due to their good tabletability and fast dissolution rate, while dextrans with higher molecular weights could be an efficient disintegrant due to their swelling ability. [ABSTRACT FROM AUTHOR]

Purpose: This work investigated the influence of a model protein, bovine serum albumin (BSA), on the properties of a thermogelling formulation intended for administration inside body compartments where there is high albumin content, as in the case of inflamed joints; it also explored the relation between the variation of these properties and release performance of methotrexate (MTX), a drug used to treat forms of arthritis and rheumatic conditions. Methods: The influence of BSA on the micellisation and gelation behaviour of Poloxamer 407, chosen as a model copolymer, was studied by differential scanning calorimetry (microDSC), dynamic light scattering (DLS), fluorescence spectroscopy and rheology studies. A release study of MTX loaded inside the hydrogel in presence and in absence of BSA was performed. Results: DLS and microDSC data revealed that the micellisation process was not affected by the protein, as demonstrated by unaltered micellar size and thermodynamic parameters. While the presence of BSA in the copolymer system reduced gel consistency, the hydrogel release performance was only slightly affected. Conclusion: Our results suggested that the kinetics of MTX release mainly depended on the presence of the thermogelling copolymer, although other mechanisms related to BSA could be involved. Finally, the study assessed the feasibility of using a thermogelling hydrogel for in situ drug administration in areas with the presence of high protein concentrations. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop and evaluate a delivery system comprising a thermosensitive gel for the sustained release of steroidal hormones in fish, over an extended period of time after a single intramuscular ( i.m. ) injection and for the improved reproductive performance in fish. Controlled delivery systems based on thermosensitive gels are easy to prepare, low cost and high versatility dosage forms, which have been shown to be effective in several animal species for sustained release of hormones. In this work, a thermosensitive gel system based on poloxamer 407 in water:ethanol medium, able to work as a prolonged release carrier for 17β-estradiol (E2), has been developed. Such a system was able to solubilize the lipophilic E2 and to gel at the required water temperature for fish rearing (20 °C). Moreover, the system exhibited the best injection condition at temperatures below 15 °C when the system behaved as a low viscosity Newtonian liquid. The thermosensitive gel system was tested in vivo in the fish model, Carassius auratus , and the results compared with a single i.m. injection of E2 dissolved in corn-oil and other relevant control systems not containing E2. The results were particularly interesting, since fish injected with the E2 thermosensitive gel formulation, showed significantly higher levels of the circulating hormone than corn oil-E2 treated animals at 72 and 96 h after injection. In addition, the thermogel system was able to sustain the plasma level of E2 for about 11 days. The increased plasma levels of E2 were also accompanied by maintained higher values of plasma vitellogenin (VTG), thus suggesting that the thermosensitive polymer based delivery system could prevent rapid hepatic clearance of E2, resulting in prolonged stimulation of estrogen receptor-mediated pathways in goldfish. [ABSTRACT FROM AUTHOR]

PLGA-PEG-PLGA are copolymers, able to form temperature-dependent hydrogels or sol dispersions at selective conditions. A general overview about the rheological characterization of their aqueous dispersions, focusing how the structural characteristics (e.g. molecular weight, PEG/PLGA ratio) affect their temperature-dependent behaviour, is presented. Different PLGA-PEG-PLGA were synthesized by varying the amount of lactide and glycolide and the amount and molecular weight of PEG. All polymers were characterized by gel-permeation chromatography and differential scanning calorimetry. Then, polymeric dispersions in water (15%–25% w/w) were analysed by oscillatory rheological measurements. At solid state, all copolymers are amorphous and the calculated glass transition temperatures were dependent on PEG/PLGA ratio. As regard aqueous dispersions, the temperature-dependent rheological behaviour named "partially thermogelling" has been described, in addition to the commonly reported thermogelling one. In these samples, the consistency increases over temperature without forming a three-dimensional network as for real hydrogels. All rheological characteristics can be explained according to the proposed categorization (thermogel, partial thermogel and sol dispersion). Image 1 • All PLGA-PEG-PLGA copolymers are amorphous; T g values were dependent on the PEG/PLGA. • Aqueous dispersions were categorised in terms of temperature-dependent behaviour. • Partial thermogelling, thermogelling and sol rheological behaviours were described. • In partially thermogels, consistency increases over temperature without a 3D network. • Thermogels were observed for copolymers having a PEG/PLGA ratio around 0.45–0.5. [ABSTRACT FROM AUTHOR]

The coating process for solid dosage forms is widely used in the pharmaceutical industry but presents challenges for small-scale production, needed in personalized medicine and clinical or galenic settings. This study aimed to evaluate immersion coating, a cost-effective small-scale method, for enteric-coated gelatin capsules using standard equipment. Two enteric coating polymers and different polymer concentrations were tested, along with API solubility. Results were compared with commercially available enteric capsule shells. Successful preparation of enteric coating capsules via immersion necessitates a comprehensive grasp of API and enteric polymer behavior. However, utilizing commercially available enteric capsule shells does not guarantee ease or robustness, as their efficacy hinges on the attributes of the active ingredient and excipients. Notably, coating with Eudragit S100 stands out for its superior process robustness, requiring minimal or no development time, thus representing the best option for small-scale enteric capsule production. [ABSTRACT FROM AUTHOR]

Carlina acaulis root essential oil (EO) is one of the most potent mosquito larvicides (LC50 < 2 ppm). This EO is mainly composed of carlina oxide (> 90%). Poor water solubility and rapid degradation from UV light and oxygen in the environment limit the real-world use of this EO. Herein, we developed nanocarrier-based formulations, namely micro- and nanoemulsions (ME and NE, respectively) containing C. acaulis EO or carlina oxide (both at 0.5%) as active ingredients (a.i.). The larvicidal activity of ME and NE was evaluated against Culex quinquefasciatus. The highest larvicidal activity was achieved by the ME containing 0.5% of the EO (M1); its LC50(90) was 579.1 (791.3) µL L−1. Sublethal effects of this ME and its a.i. were assessed testing both at the LC16, LC30, LC50 and LC90 on mosquito larvae exposed to each product for 1–7 h, and then monitoring mortality for 18 days. At variance with the EO, ME application, even at LC16, led to 100% mortality at 18 days. The EO and its encapsulated form were scarcely toxic to human keratinocytes (HaCaT) and human fibroblast (NHF A12) cell lines. The acute toxicity of C. acaulis EO and its ME (M1) was also evaluated in Wistar rats through oral administration; EO LD50 was 1098 mg kg−1 bw, whereas its ME, even at 5000 mg kg−1 bw (considered the upper testing limit to establish safety to mammals), was not toxic. This study highlights the outstanding efficacy of C. acaulis EO ME for developing long-lasting and safe larvicides against Cx. quinquefasciatus. [ABSTRACT FROM AUTHOR]

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson's disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson's disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson's disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing. [ABSTRACT FROM AUTHOR]

Industrial hemp (Cannabis sativa L.), due to its bioactive compounds (terpenes and cannabinoids), has gained increasing interest in different fields, including for medical purposes. The evaluation of the safety profile of hemp essential oil (EO) and its encapsulated form (nanoemulsion, NE) is a relevant aspect for potential therapeutic applications. This study aimed to evaluate the toxicological effect of hemp EOs and NEs from cultivars Carmagnola CS and Uso 31 on three cell lines selected as models for topical and inhalant administration, by evaluating the cytotoxicity and the cytokine expression profiles. Results show that EOs and their NEs have comparable cytotoxicity, if considering the quantity of EO present in the NE. Moreover, cells treated with EOs and NEs showed, in most of the cases, lower levels of proinflammatory cytokines compared to Etoposide used as a positive control, and the basal level of inflammatory cytokines was not altered, suggesting a safety profile of hemp EOs and their NEs to support their use for medical applications. [ABSTRACT FROM AUTHOR]

Isofuranodiene is a bioactive furanosesquiterpene occurring as the major volatile compound in the essential oil from Smyrnium olusatrum (Apiaceae). It has a notable potentiality to be used as a botanical insecticide. However, its low solubility together with susceptibility to oxidation and thermal degradation limits its application on a wide scale. To face these challenges, isofuranodiene was encapsulated in stable microemulsions (MEs) at two concentrations (ME 750: 0.75%, ME 375: 0.375%). We assessed the larvicidal activity in the short term and after several days of exposure of pure isofuranodiene and its MEs against the filariasis vector Culex quinquefasciatus. The impact of ME-based larvicide at sublethal concentrations on adult emergence was evaluated. Finally, to shed light on potential ecotoxicology risks for nontarget invertebrates, MEs were tested on the aquatic microcrustacean Daphnia magna and on the earthworm Eisenia fetida. Pure isofuranodiene and S. olusatrum leaf essential oil, used as controls, showed their potential as mosquito larvicidal agents (LC50 of 29.2 and 18.6 μL L−1, respectively). Isofuranodiene formulated in ME 750 was effective against C. quinquefasciatus larvae, leading to significant larval mortality over time and a marked decrease in adult emergence. Both isofuranodiene MEs showed little impact on the nontarget aquatic microcrustacean Daphnia magna (ME 750 and ME 375: mortality < 19% after 48 h of exposure at 32 mL L−1 and 20 mL L−1, respectively) as well as on earthworms (ME 750 and ME 375: no mortality and mortality < 7% after 14 days of exposure to 1000 mg kg−1, respectively), outlining their potential employ in vector control operations. [ABSTRACT FROM AUTHOR]

Doxil ® is a stealth marketed PEGylated liposomal formulation, containing the anticancer drug doxorubicin. After loading via a pH gradient, fibrillar supramolecular structures of doxorubicin sulfate originates inside the core of the liposomes. Recently, the crystallinity of doxorubicin sulfate has been confirmed by high-resolution calorimetry. However, no detailed information are available on the nature of doxorubicin sulfate nanocrystals and on the effect of different thermal treatments. Thus, the aim of this work was to characterize the thermal behaviour of Doxil ® in comparison to the unloaded liposomes using microcalorimetry, dynamic light scattering and high-resolution ultrasound spectroscopy (HR-US). Different thermal programmes were applied with the aim to highlight the effect of the treatments on the formulation. The used techniques confirmed the ordered state of doxorubicin nanocrystals inside PEGylated liposomes. Particularly, microcalorimetry and HR-US highlighted the changes in the thermal behaviour of the drug under different heating programmes. Doxorubicin nanocrystals were found to be stable after heating up to 80 °C, but an irreversible thermal behaviour was observed after a prolonged heating at elevated temperature (2 h at 80 °C). The non-reversibility could be related to the formation of a different ordered structure and enhanced by the slight leakage of the drug occurring after a prolonged heating. [ABSTRACT FROM AUTHOR]

The use of surfactants as drug permeability enhancers across epithelial barriers remains a challenge. Although many studies have been performed in this field using synthetic surfactants, the possibility of employing surfactants produced by bacteria (the so called biosurfactants”) has not been completely explored. Among them, one of the most well characterized class of biosurfactants are rhamnolipids. The aim of the study was to investigate the effect of rhamnolipids on the epithelial permeability of fluorescein isothiocyanate-labelled dextrans 4 kDa and 10 kDa (named FD4 and FD10, respectively) as model for macromolecular drugs, across Caco-2 and Calu-3 monolayers. These cell lines were selected as an in vitro model for the oral and respiratory administration of drugs. Before performing permeability studies, rhamnolipids mixture was analysed in terms of chemical composition and quantification through mass analysis and HPLC. Cytotoxicity and transepithelial electrical resistance (TEER) studies were also conducted using Caco-2 and Calu-3 cell lines. A dose-dependent effect of rhamnolipids on TEER and FD4 or FD10 permeability across both cell lines was observed at relatively safe concentrations. Overall, results suggest the possibility of using rhamnolipids as absorption enhancers for macromolecular drugs through a reversible tight junction opening (paracellular route), despite more investigations are required to confirm their mechanism of action in term of permeability. [ABSTRACT FROM AUTHOR]

This study has investigated the potential use of zein protein from corn as a pharmaceutical excipient for formulation of oral controlled-release matrices. SMCC (silicified microcrystalline cellulose)-Prosolv® 90, SMCC HD-Prosolv® 90 HD, Avicel® PH 102 and Mannitol 60 were evaluated as co-excipients to improve the processability of zein powder. Zein/SMCC-Prosolv® 90 blend had the best flowability and tabletability. Tablets with tramadol hydrochloride, zein and SMCCProsolv® 90 were prepared by direct compression. Drug release from the tablets was measured by dissolution testing. The dissolution profiles obtained were compared using the dissolution efficiency (DE) and were fitted to the Korsmeyer–Peppas equation. Controlled drug release, governed by anomalous (non-Fickian) drug transport, was obtained over the test duration. Drug release rate and mechanism were dependent on formulation parameters, such as tablet hardness, zein/SMCC ratio and drug loading, as well as medium pH. Dynamics of tablets swelling correlated well with drug release rate and mechanism, with faster drug release and greater contribution of polymer relaxation being obtained at increased swelling. In conclusion, the present work has shown that zein/SMCC based matrix formulation can be used as a new platform for oral-controlled drug delivery which can be easily customized by adjusting formulation parameters. The use of this formulation could be attractive for customers and manufacturers who prefer to avoid synthetic or chemically modified excipients. [ABSTRACT FROM AUTHOR]

Purpose: Biodegradable polymeric nanoparticles of different architectures based on polyethylene glycol-co-poly(ε-caprolactone) block copolymers have been loaded with noscapine (NOS) to study their effect on its anticancer activity. It was intended to use solubility of NOS in an acidic environment and ability of the nanoparticles to passively target drugs into cancer tissue to modify the NOS pharmacokinetic properties and reduce the requirement for frequent injections. Methods: Linear and star-shaped copolymers were synthetized and used to formulate NOS loaded nanoparticles. Cytotoxicity was performed using a sulforhodamine B method on MCF-7 cells, while biocompatibility was determined on rats followed by hematological and histopathological investigations. Results: Formulae with the smallest particle sizes and adequate entrapment efficiency revealed that NOS loaded nanoparticles showed higher extent of release at pH 4.5. Colloidal stability suggested that nanoparticles would be stable in blood when injected into the systemic circulation. Loaded nanoparticles had IC values lower than free drug. Hematological and histopathological studies showed no difference between treated and control groups. Pharmacokinetic analysis revealed that formulation P1 had a prolonged half-life and better bioavailability compared to drug solution. Conclusions: Formulation of NOS into biodegradable polymeric nanoparticles has increased its efficacy and residence on cancer cells while passively avoiding normal body tissues. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A dietary supplement potentially employed for the treatment and/or prevention of hyperlipidemia was developed. The proposed product is composed of a combination of natural macromolecules as chitosan (CH), α-cyclodextrin (α-CD), and lupin proteins (LP). First, the anti-hyperlipidemic effect of the α-CD and LP binary mixture was assessed and compared to that of the extensively utilized anti-hyperlipidemic CH, using a hyperlipidemic rat model. The anti-hyperlipidemic effect of their combination was also demonstrated. Additionally, ligand–target and protein–protein docking studies were performed. The in vivo results displayed that on intergroup comparison, blending CH, α-CD, and LP promised a superior therapeutic effect over α-CD and LP mixture, CH, and the marketed atorvastatin, potentiating a considerable reduction of serum lipid profile and the calculated atherogenic risk predictor indices. Molecular docking study revealed a weak hydrophobic cholesterol–CH and cholesterol–α-CD interactions, while protein–protein docking study showed a good lipase–LP interaction, involving eight hydrogen bonds. Then, on the base of the in vivo and docking study results, a tablet formulation was produced aimed to overcome the negative technological effects of the anti-hyperlipidemic macromolecules: long disintegration time and tablets mechanical resistance. The optimized tablet formulation has a disintegration time shorter than 15 min and a weight loss from friability test lower than 1%, which are in line with the regulatory specifications for uncoated tablets. Overall, this anti-hyperlipidemic formulation is attractive for the dietary and nutraceutical market, despite further clinical studies are required to assess the efficacy, possible side effects, and product compliance. [ABSTRACT FROM AUTHOR]

The aim of this research was to prepare novel block copolymer-surfactant hybrid nanosystems using the triblock copolymer Pluronic 188, along with surfactants of different hydrophilic to lipophilic balance (HLB ratio—which indicates the degree to which a surfactant is hydrophilic or hydrophobic) and thermotropic behavior. The surfactants used were of non-ionic nature, of which Tween 80® and Brij 58® were more hydrophilic, while Span 40® and Span 60® were more hydrophobic. Each surfactant has unique innate thermal properties and an affinity towards Pluronic 188. The nanosystems were formulated through mixing the pluronic with the surfactants at three different ratios, namely 90:10, 80:20, and 50:50, using the thin-film hydration technique and keeping the pluronic concentration constant. The physicochemical characteristics of the prepared nanosystems were evaluated using various light scattering techniques, while their thermotropic behavior was characterized via microDSC and high-resolution ultrasound spectroscopy. Microenvironmental parameters were attained through the use of fluorescence spectroscopy, while the cytotoxicity of the nanocarriers was studied in vitro. The results indicate that the combination of Pluronic 188 with the above surfactants was able to produce hybrid homogeneous nanoparticle populations of adequately small diameters. The different surfactants had a clear effect on physicochemical parameters such as the size, hydrodynamic diameter, and polydispersity index of the final formulation. The mixing of surfactants with the pluronic clearly changed its thermotropic behavior and thermal transition temperature (Tm) and highlighted the specific interactions that occurred between the different materials, as well as the effect of increasing the surfactant concentration on inherent polymer characteristics and behavior. The formulated nanosystems were found to be mostly of minimal toxicity. The obtained results demonstrate that the thin-film hydration method can be used for the formulation of pluronic-surfactant hybrid nanoparticles, which in turn exhibit favorable characteristics in terms of their possible use in drug delivery applications. This investigation can be used as a road map for the selection of an appropriate nanosystem as a novel vehicle for drug delivery. [ABSTRACT FROM AUTHOR]

BACKGROUND: Solvent‐free microwave‐assisted extraction (MAE) is a green extraction method capable of boosting the yield and quality profile of hemp essential oil when compared with other conventional extraction techniques. During this process, two by‐products are produced, namely the aqueous residue containing bioactive phenolics and the residual deterpenated biomass, which can be used for further extraction and purification of phytocannabinoids. To date, the hemp industry has not utilized these products, although they can be valuable for the food, cosmetic, nutraceutical and pharmaceutical market. RESULTS: This study assessed and optimized the variables affecting MAE efficiency, namely microwave irradiation power, extraction time and added water, which were studied using a central composite design approach, and results were used to optimize the extraction process for recovering three valuable fractions: essential oil, polyphenols and phytocannabinoids. The products obtained using the optimized conditions were characterized in terms of yield, chemical profile and antioxidant potential. Moreover, the by‐products obtained during the optimized run were further analyzed in terms of their biological activity using both enzymatic and non‐enzymatic assays. The aqueous residue demonstrated a powerful α‐glucosidase inhibition, a good activity in terms of superoxide radical scavenging activity, a modest efficacy in terms of inhibition of advanced glycation end products formation and no activity in terms of lipase inhibition. The residual deterpenated biomass did not possess significant biological activity. CONCLUSION: This work demonstrated valorization of industrial hemp essential oil and its by‐products, obtained by a sustainable and eco‐friendly extraction method, through an almost waste‐free approach. Cannabinoids as well as other valuable bioactive compounds such as glycosidic flavones may be recovered from the residues of the essential oil extraction, representing interesting substances in the pharmaceutical, cosmetic and nutraceutical fields. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Essential oils (EOs) represent innovative and safe botanical pesticides to be exploited in different fields, including agriculture, being often obtained by cheap and easily available plant crops. However, their use is threatened by some limits, which are mainly linked to their physico-chemical properties. In this regard, the use of nanoemulsions (NEs) usually enables to overcome these limits but often also to improve the biological activities of these products. Bunium persicum (Boiss.) B Fedtsch. and Ziziphora clinopodioides Lam. are two aromatic plants of economic interest well known for their traditional food and medical uses. Their EOs exhibited several biological properties, including a remarkable insecticidal activity against different targets. Here, the chemical analysis of the two EOs revealed the predominance of γ -terpinene (35.8%), cumin aldehyde (16.6%), γ -terpinen-7-al (14.0%), and α -terpinen-7-al (11.7%) for B. persicum , and pulegone (55.6%), piperitenone (12.8%), and iso -menthone (8.0%) for Z. clinopodioides. NEs were successfully obtained by high-pressure homogenization or ultrasonication method, using polysorbate 80 as emulsifier. The EOs and their 10% NEs were evaluated against larvae and pupae of Culex quinquefasciatus Say mosquitoes. In detail, both EOs exhibited a good larvicidal efficacy (LC 50 of 35.8 and 68.9 µL L−1 for B. persicum and Z. clinopodioides , respectively). Bunium persicum EO NE showed higher efficacy than the EO alone (LC 50 = 290.4 µL L−1), considering that only the 10% of the EO was encapsulated. Conversely, Z. clinopodioides NE showed the same efficacy than the EO alone (LC 50 of 759.8 µL L−1). In addition, both NEs displayed significantly better sublethal toxicity compared with the EOs. Moreover, even if no significant mortality was detected in the pupal stage, only 12% of the larvae pupated and emerged as adults in the case of the NE from B. persicum. In conclusion, both EOs and their NEs could be promising candidates for the development of botanical pesticides, also considering the commercial availability and affordability of these EOs. • Bunium persicum and Ziziphora clinopodioides are valuable sources of essential oils. • Their nanoemulsions were obtained by obtained by high-pressure homogenization. • Nanoemulsions evaluated for toxicity and sublethal effects on Culex quinquefasciatus. • Nanoemulsions showed same contact toxicity than essential oils alone. • Nanoemulsions showed better sublethal toxicity than essential oils. [ABSTRACT FROM AUTHOR]

High-resolution ultrasound spectroscopy (HR-US) is a spectroscopic technique using ultrasound waves at high frequencies to investigate the structural properties of dispersed materials. This technique is able to monitor the variation of ultrasound parameters (sound speed and attenuation) due to the interaction of ultrasound waves with samples as a function of temperature and concentration. Despite being employed for the characterization of several colloidal systems, there is a lack in the literature regarding the comparison between the potential of HR-US for the determination of phospholipid thermal transitions and that of other common techniques both for loaded or unloaded liposomes. Thermal transitions of liposomes composed of pure phospholipids (dimyristoylphosphatidylcholine, DMPC; dipalmitoylphosphatidylcholine, DPPC and distearoylphosphatidylcholine, DSPC), cholesterol and their mixtures were investigated by HR-US in comparison to the most commonly employed microcalorimetry (mDSC) and dynamic light scattering (DLS). Moreover, tramadol hydrochloride, caffeine or miconazole nitrate as model drugs were loaded in DPPC liposomes to study the effect of their incorporation on thermal properties of a phospholipid bilayer. HR-US provided the determination of phospholipid sol-gel transition temperatures from both attenuation and sound speed that are comparable to those calculated by mDSC and DLS techniques for all analysed liposomal dispersions, both loaded and unloaded. Therefore, HR-US is proposed here as an alternative technique to determine the transition temperature of phospholipid membrane in liposomes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Microwave extraction enhanced spilanthol content in Acmella oleracea essential oil. • Spilanthol was isolated and used for comparative purposes. • The essential oil was encapsulated into a nanoemulsion. • Its acute toxicity and impact on fertility were evaluated on Culex quinquefasciatus. • Cytotoxicity and anti-inflammatory effects were determined in human cells. Acmella oleracea (L.) R.K. Jansen, also named jambù, is an edible and medicinal plant native to Brazil but extensively cultivated all over the world due to its diverse utilizations in food, cosmetics, pharmaceutics, and pest management science. Most of applications are related to the presence of active ingredients, namely alkylamides, among which spilanthol is the most important one. On the other hand, the plant biomass resulting from the large-scale cultivation of A. oleracea may yield an essential oil (EO), which can be used for some industrial purposes, for instance as larvicide against vector mosquitoes. This EO is mainly characterized by mono- and sesquiterpenes, however also spilanthol can be detected in the mixture. To maximize the content of spilanthol in the A. oleracea EO, A. oleracea aerial parts obtained from a cultivation in central Italy were subjected to microwave-assisted extraction (MAE). This procedure allowed to obtain a higher yield and spilanthol content when compared with traditional hydrodistillation (0.47 v 0.22 %, and 13.31 vs 2.24 %, respectively). The EO terpene fraction was mainly represented by β- pinene (10.8 %), myrcene (12.3 %), (E)-caryophyllene (19.4 %) and α- humulene (1.1 %). The A. oleracea EO was encapsulated into a nanoemulsion (NE) containing 6 % EO using a high-energy method. The formulation physical stability was assessed by optical microscope and DLS analyses at different timepoints showing stability up to one year of storage. The A. oleracea EO and its NE, along with the isolated spilanthol, were evaluated for acute toxicity against the 3rd instar larvae of Culex quinquefasciatus , a filariasis and arbovirus vector of public health importance, achieving LC 50 values of 16.1, 407.5, and 3.1 μL/L, respectively. The larvicidal activity seemed to be not dependent on the interaction with the cholinergic system, as shown by the high IC 50 values of A. oleracea EO and spilanthol exhibited in the anti-acetylcholinesterase (AChE) assay. Testing LC 30 values, the A. oleracea -borne products showed a significant impact on larval development, fecundity, fertility and natality of C. quinquefasciatus. Testing LC 30 values, the A. oleracea EO-NE provided a higher efficacy than spilanthol, reducing the adult fertility, in terms of egg hatchability (%) and the overall abundance of F 1 larvae. These results can be considered as promising for the development of new mosquito larvicides. The safety use of A. oleracea EO, NE and spilanthol was demonstrated in assays on mammalian fibroblasts and microglia cells, showing low level of cytotoxicity coupled with protective effects against inflammation. [ABSTRACT FROM AUTHOR]

[Display omitted] • The development of green insecticides for real-world use is a major challenge. • This review focuses on Apiaceae-borne botanicals effectiveness against mosquitoes. • Essential oils and main constituents as mosquitocidal/repellent agents are reviewed. • Modes of action of Apiaceae essential oils and their major compounds are discussed. • Toxicity on non-target species and micro/nano-formulation development is analysed. Apiaceae is a family encompassing medicinal and aromatic plants. They produce essential oils (EOs) inside oil canals, known as ducts and vittae, which occur in their vegetative and reproductive organs. Given the high EO yields and the availability of raw material from cultivations widespread all over the world, Apiaceae are exploitable for different industrial applications. An interesting perspective is their utilization in the fabrication of botanical insecticides effective against insect vectors of public importance such as mosquitoes, aiming to be eco-friendly alternatives to synthetic insecticides. On this basis, in the current review, we collected scientific evidence supporting the use of Apiaceae EOs and their major constituents as active ingredients in insecticidal formulations against larvae and adults of several mosquitoes that are important pathogen vectors (e.g., Anopheles , Aedes and Culex species). For this purpose, we analysed the published data on their larvicidal, ovicidal, oviposition deterrent, pupicidal, adulticidal, and repellent effects, using efficacy thresholds as in the case of larvicidal activity (LC 50 (lethal concentration killing 50 % of the exposed population) < 50 ppm). Toxicity to non-target organisms, including vertebrates, has also been reviewed. The major EO constituents have been highlighted, each with its spectrum of mosquitocidal activity, providing insights on their multiple modes of action. The urgent need to develop highly stable micro/nano-formulations for real-world use has been outlined. Current weaknesses and strengths in the steps toward the development of botanical insecticides have been analysed to increase awareness of the future challenges necessary to open the doors to the industrial utilization of Apiaceae EOs by agrochemical companies. [ABSTRACT FROM AUTHOR]

• mPEG-PLGA NPs, loaded with saquinavir mesylate (SQV), were incorporated inside carbopol (C974)-based hydrogel as a vaginally administered prevention or therapeutic treatment for HIV infection. • Hydrogel consistency was reduced by increasing NPs amount at a fixed C974 concentration. • mPEG-PLGA NPs had a relevant effect in promoting the incorporation of the drug inside hydrogel despite its moderate loading. • As a consequence, the incorporation NPs in the formulation led to a higher amount of the drug released from the hydrogel, using an immersion cell release apparatus. • The in vitro findings of the study could have an impact also on the in vivo bioavailability of the drug. Saquinavir mesylate (SQV) is a protease inhibitor commonly employed for the treatment of human immunodeficiency virus-1 infection. It is generally administered orally as tablets in combination with other antiviral drugs. Another promising route of administration can be represented by the vaginal one through topically applied formulations. This delivery can reduce the first-pass effect in the case of systemic drug adsorption or prevent HIV infection. We propose the formulation of a Carbopol® 974 (C974) hydrogel containing biodegradable mPEG-PL(L)GA nanoparticles (NPs) for the vaginal delivery of SQV, intended both as a prevention and a therapeutic strategy. mPEG-PL(L)GA NPs were incorporated into the C974 polymeric matrix, leading to a reduction of the hydrogel consistency dependent on NPs and C974 concentrations. Despite the moderate drug loading into NPs, the presence of the NPs had an impact on the in vitro release of the drug from the hydrogel at pH 5.5 using immersion cells. A higher amount of the drug was released, probably due to the effect of NPs in promoting the incorporation of the drug into the hydrogel at a high SQV dose. These findings can be useful for the development of topically applied hydrogels for SQV delivery, possibly having improved in vivo therapeutic outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

Formulation development and non-target effect studies are two crucial steps for the registration of new botanical insecticides. Previous reports put in evidence the potential of hemp (Cannabis sativa L.) essential oil (EO) as a new candidate ingredient for developing green insecticides. However, the validation of its target and non-target effects after proper encapsulation is missing so far. In the current work, we investigated the insecticidal efficacy of the EO obtained from the hemp variety 'Kompolti', and we optimized its formulation development into a nanoemulsion (NE). The latter was assayed against larvae of Culex quinquefasciatus Say, a well-known vector of Wuchereria bancrofti Cobbold, avian malaria, and several arboviruses, such as Western equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, and Zika virus. Considering the percentage of encapsulated EO (7.5% w/w), the developed NE showed mortality on Cx. quinquefasciatus larvae, in terms of LC 50(90) values [72.2 (207.2) ppm], like those of pure EO [50.8(142.3) ppm]. Non-target toxicity experiments showed limited toxicity on the aquatic microcrustacean Daphnia magna Straus (i.e., mortality <16% after 48 h of exposure to the EO-based NE at the LC 90 estimated on mosquito larvae). Considering that the LC 50 values detected in this study are lower than those belonging to many EOs, and that the application at sublethal doses caused mortality between 39.1% and 40.8% as well as a reduction in mosquito fertility resulting in a reduction in natality of 40.4% and 45.1% for the EO and EO-based NE, respectively, both products may be considered as potential environmentally friendly and sustainable insecticides. [Display omitted] • Kompolti hemp essential oil was encapsulated in nanoemulsions. • The insecticidal efficacy of hemp essential oil and its nanoemulsion was assessed. • Both formulations had high acute toxicity on Culex quinquefasciatus larvae. • Both products had limited impact on the aquatic microcrustacean Daphnia magna. [ABSTRACT FROM AUTHOR]

Amphiphilic polymers represent one of the main class of stabilizers for non-lamellar lyotropic liquid crystalline nanoparticles, being essential for their formation and stability. In the present study, poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO- b -PCL) block copolymers and poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline) (MPOx) gradient copolymers were incorporated as stabilizers in liquid crystalline nanoparticles prepared from glyceryl monooleate. The polymers were chosen according to their high biocompatibility and promising stealth properties, in order to develop safe and efficient drug delivery nanosystems. The physicochemical characteristics and fractal dimension of the resultant nanosystems were obtained from light scattering techniques, while their micropolarity and microfluidity from fluorescence spectroscopy. The effect of temperature, serum proteins and ionic strength on the physicochemical behavior was monitored. Their morphology was assessed by cryo-TEM, while their thermal behavior by microcalorimetry and high-resolution ultrasound spectroscopy. Their properties were dependent on the stabilizer chemistry and topology (block/gradient copolymer) and its concentration. Subsequently, resveratrol, as model hydrophobic drug, was loaded into the nanosystems, the entrapment efficiency was calculated and in vitro release studies were carried out, highlighting how the different stabilizer can differentiate the drug release profile. In conclusion, the proposed copolymers broaden the toolbox of polymeric stabilizers for the development of liquid crystalline nanoparticles intended for drug delivery applications. [ABSTRACT FROM AUTHOR]

• Hemp essential oil was obtained by microwave-assisted extraction. • The operative conditions were optimized using a central composite design. • CBD-enriched essential oil can be obtained by MAE optimization. • Hydrodistillation was carried out for comparative purposes. • The enantiomeric ratio of chiral terpenes was determined. The increase of cultivation of industrial hemp (Cannabis sativa L.) all over the world offers new opportunities for the industry to manufacture innovative products from this multipurpose crop. In this regard, the hemp essential oil represents a niche product with potential interest for the pharmaceutical, nutraceutical, cosmeceutical and agrochemical companies. On this basis, in the present work we used the microwave-assisted extraction (MAE) to get an essential oil enriched in bioactive compounds, especially cannabidiol (CBD), from the dry inflorescences of the Italian variety CS (Carmagnola Selezionata). For this purpose, the operative conditions to increase the essential oil yield and CBD concentration in terms of microwave irradiation power (W/g), extraction time (min) and water added to the plant matrix after moistening (%), were optimized using a central composite design (CCD) approach using a Milestone ETHOS X device. The conventional hydrodistillation (HD) performed for 240 min was used for comparative purposes. The qualitative compositions of essential oils obtained by MAE and HD were analysed by GC-MS, whereas the quantitative detection of CBD and main terpenoids (α-pinene, β-pinene, myrcene, limonene, terpinolene, (E)-caryophyllene, α-humulene and caryophyllene oxide) was achieved by GC-FID. Furthermore, the enantiomeric distribution of the chiral constituents (α-pinene, β-pinene, limonene, (E)-caryophyllene and caryophyllene oxide) was determined using chiral chromatography. Results showed that the MAE treatment, using high irradiation power and relatively long extraction times, increased significantly the content of CBD in the essential oil while maintaining high oil yield values when compared with conventional HD. The enantiomeric excess of three chiral monoterpenes (α-pinene, β-pinene and limonene) was determined, with the (+)-enantiomers being predominant, whereas (E)-caryophyllene and caryophyllene oxide were enantiomerically pure. In conclusion, the MAE was successfully applied to hemp dry inflorescences in order to obtain a CBD-rich essential oil which may be exploited in several industrial applications. [ABSTRACT FROM AUTHOR]

The interest around essential oils is constantly increasing thanks to their biological properties exploitable in several fields, from pharmaceuticals to food and agriculture. However, their widespread use and marketing are still restricted due to their poor physico-chemical properties; i.e., high volatility, thermal decomposition, low water solubility, and stability issues. At the moment, the most suitable approach to overcome such limitations is based on the development of proper formulation strategies. One of the approaches suggested to achieve this goal is the so-called encapsulation process through the preparation of aqueous nano-dispersions. Among them, micro- and nanoemulsions are the most studied thanks to the ease of formulation, handling and to their manufacturing costs. In this direction, this review intends to offer an overview of the formulation, preparation and stability parameters of micro- and nanoemulsions. Specifically, recent literature has been examined in order to define the most common practices adopted (materials and fabrication methods), highlighting their suitability and effectiveness. Finally, relevant points related to formulations, such as optimization, characterization, stability and safety, not deeply studied or clarified yet, were discussed. [ABSTRACT FROM AUTHOR]

Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) in drug delivery is advantageous compared to polymers derived from fossil fuels. The present work aimed to produce microparticles (MPs) derived from novel sustainable polymers, loaded with triamcinolone acetonide (TA) for treatment of rheumatoid arthritis via intra-articular (IA) delivery. PDL was synthesized from green δ-decalactone monomers and co -polymerized with methoxy-polyethylene glycol (mPEG) forming PEG-PDL with different molecular weights. The Hansen's solubility parameters were applied to select the most compatible polymer with the drug. An o/w emulsion/solvent evaporation technique was used for MPs fabrication, using 3 [ 3 ] full factorial design. Selection of the optimized MPs was performed using Expert Design® software's desirability function. The optimized formulations were characterized using scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro release studies. The inhibition percents of inflammation and histopathological studies were assessed in complete Freund's adjuvant-induced rats' knee joints evaluating the effect of IA injections of selected MPs compared to the free drug suspension. Solubility studies revealed high compatibility and miscibility between TA and PEG-PDL 1700 , which was blended with PLA for convenient MPs formation. The in vitro characterization studies confirmed the formation of drug-copolymer co-crystals. The in vivo studies ensured the superiority of the newly designed composite MPs in inflammation suppression, compared to the free drug suspension and PLA MPs as well. The present study proved the advantage of using sustainable polymers in a novel combination for effective drug delivery and suggesting its usefulness in designing versatile platforms for therapeutic applications. Unlabelled Image • Six different PEG-PDL copolymers were synthesized using ring opening polymerization. • Hansen's solubility parameters confirmed high drug–copolymer compatibility. • TA-loaded PLA/PEG-PDL MPs were developed and optimized via a statistical design. • In vitro characterization studies endorsed the formation of TA-copolymer co-crystal. • The composite MPs showed a sustained anti-inflammatory action in rats' arthritic joints. [ABSTRACT FROM AUTHOR]

[Display omitted] Lubricants are excipients used in tablet formulations to reduce friction and adhesion forces within the die or on the punches surface during the manufacturing process. Despite these excipients are always required for the tablets production, their amount must be carefully evaluated since lubricants can negatively impact on mechanical strength, disintegration and dissolution behavior of solid dosage forms. Alternative compounds have been suggested to overcome the issues of conventional lubricants and sodium lauryl sulfate (SDS) is one of the most promising one. Despite SDS has been object of several investigations, a definitive conclusion on its effectiveness cannot still be drawn. Particularly, its efficacy on tablets disaggregation and API dissolution is still unclear. Here, the effect of SDS on all the relevant features of tablets and tableting process has been evaluated on immediate release hydrophobic tablets formulations in comparison with conventional lubricants. The results of this investigation are quite outspoken: SDS has a low lubricant power while it determines only a limited improvement on tablets hardness. It greatly improves the tablets wettability but only on model formulations, the presence of superdisintegrants resets its effectiveness and any possible effect on tablets disaggregation. None of the tested formulations showed improvement on the API dissolution rate. [ABSTRACT FROM AUTHOR]

Press-coating (also called compression coating or dry coating) consists of a second compression of an outer layer of material over a preformed tablet core. Despite being old, this technology has returned to popularity due to its widespread use in preparation of chronotherapeutic dosage forms. The literature available on press-coated tablets has mainly investigated drug release kinetics, while there is a lack of information about their mechanical properties. Here we study, for the first time, the effect of material properties and manufacturing parameters on the mechanical characteristics of press-coated tablets. Firstly, we show that the stiffness of the bare core tablets depends on the material type and, in case of viscoelastic materials, also depends on the compression pressure. We then demonstrate that less stiff (i.e. more viscoelastic) core tablets deform to a greater extent upon the second compression and thus allow the formation of less porous, harder coats and with a more homogenous density distribution. Finally, we find that changes in the mechanical properties of press-coated tablets over one month storage are almost negligible. Our data suggest that viscoelastic rather than stiff cores should be used in dry coating, as they promote the formation of more homogenous coats and with better mechanical properties. Unlabelled Image [ABSTRACT FROM AUTHOR]

Surfactants are versatile excipients, which are commonly employed in several pharmaceutical formulations as emulsifiers, stabilizing or solubilizing agents. In this field, current research is aimed at the design or discovery of amphiphilic molecules with improved characteristics in terms of safety (toxicological profile) and biological activities (e.g. antimicrobial activity, interaction with biomembranes). Quaternary ammonium surfactants derived from amino acids are one such class of compounds with significant potential for pharmaceuticals. In this work, quaternary ammonium surfactants derived from the amino acids leucine and methionine and esterified with fatty acids of different lengths (C10, C12 and C14) were synthesized. These amphiphiles were characterized in terms of critical micelle concentration (CMC) by tensiometry and conductivity measurements, cytotoxicity (MTS and LDH assay on Caco-2 and Calu-3 cell lines) and antimicrobial activity on selected Gram-positive (S. aureus and E. faecalis), Gram-negative (E. coli and P. aeruginosa) and the fungus C. albicans. The derivatives bearing a C12 or a C14 chain displayed CMC, EC 50 (from cytotoxicity assays) and minimum inhibition concentration (MIC) values that are comparable to those of benzalkonium chloride (used as reference), especially towards Gram-positive and C. albicans. On the contrary, derivatives bearing a C10 chain have higher CMC, EC 50 and MIC values, highlighting the crucial role of the hydrophobic tail in determining both physicochemical and biological properties. The C12-C14 synthesized derivatives may represent a promising alternative to benzalkonium chloride as surface active molecules and antimicrobial agents. Unlabelled Image • Quaternary ammonium cationic surfactants derived from leucine and methionine were synthesized • Physicochemical properties, cytotoxicity and antimicrobial activities are dependent on the length of the hydrocarbon chain • Derivatives with a C12 or C14 hydrocarbon chain showed cytotoxicity and antibacterial profiles comparable to BAC [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Liposomes are lamellar nanovesicles made of phospholipids of a great interest as drug delivery carriers, able to encapsulate both hydrophilic and lipophilic compounds. Some liposomal formulations have reached the market, including the doxorubicin loaded PEGylated liposomal dispersion Doxil®. The aim of the work was to investigate the possibility of concentrating liposomes through the ultrafiltration process under nitrogen pressure, using Doxil® formulation as a model. The concentrated liposomal dispersions (4x and 8x) obtained from Doxil® were characterised in terms of size evolution (dynamic light scattering), morphology (cryo-TEM) and thermal behaviour (microcalorimetry, mDSC and high-resolution ultrasonic spectroscopy, HR-US) and compared to the unloaded liposomes of the same composition. The ultrafiltration process resulted to be effective in concentrating both loaded and unloaded liposomal dispersions, which showed a particle size and thermal properties comparable to those of the non concentrated ones. Moreover, all liposomal dispersions did not show any remarkable variation in term of particle size distribution and morphology for at least 8 weeks after concentration. Altogether, results demonstrated the effectiveness in using ultrafiltration as a methodology to concentrate both loaded and unloaded liposomes without affecting the quality of the processed product. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Anise, ajowain and sea fennel essential oils (EOs) have significant mosquito larvicidal effects. • These EOs were encapsulated into stable microemulsions (MEs). • MEs were tested against Culex quinquefasciatus larvae and non-target invertebrates. • All MEs were able to exert high toxicity against mosquito larvae. • Toxicity of MEs was scarce against non-target species Daphnia magna and Eisenia fetida. Abstract The development of effective and eco-friendly pesticides to manage mosquito vector larvae is a timely and crucial challenge nowadays. Insecticide resistance is on the rise, therefore plant-borne insecticides with multiple mode of action may represent promising candidates to control insect vectors. In the present work, we encapsulated selected essential oils (EOs) from Pimpinella anisum , Trachyspermum ammi and Crithmum maritimum into highly stable microemulsions (MEs) with the aim to develop effective and eco-friendly larvicidal formulations. MEs made with both single EOs and their mixtures were tested against 3rd instar larvae of Culex quinquefasciatus, assessing acute and chronic toxicity, emergence of adults, and their impact on non-target invertebrates, i.e., Daphnia magna , Tubifex tubifex and Eisenia fetida. All MEs were able to exert toxicity against mosquito larvae, with LC 50 values in the ranges 1.45–4.01 ml L−1, along with high larval mortality and low percentage of hatched adults following short-term exposure to sublethal concentrations. Low or no mortality was observed on D. magna and E. fetida. Taken together, these results give new insights for the exploitation of plant-borne EOs as active ingredients of novel and reliable larvicidal products. [ABSTRACT FROM AUTHOR]

Hydrocolloids have been intensively investigated due to their ability to modify the rheology of the system where they are employed. They find application as thickening and gelling agents in many food, cosmetic, and pharmaceutical preparations, due to their biocompatibility and biodegradability. The present study aims to provide an exhaustive and comprehensive viscoelastic characterization of a series of hydrocolloid formulations, as function of concentration, pH, and temperature. Glucomannan, xanthan gum, tara gum, guar gum, konjac gum, and gellan gum have been analyzed at two concentrations (0.5% w/w and 1.5% w/w), using three different pH conditions (pH 1.2, 5.5, and 6.8). Their viscoelastic properties have been monitored measuring the main rheological parameters, namely, storage modulus G′ and loss modulus G′′ as function of frequency, time, and temperature. The results obtained show a clear dependence of the linear viscoelastic properties of the systems on concentration and pH, while the temperature was not a critical factor. Glucomannan, xanthan gum, tara gum, and guar gum samples prepared in phosphate buffer (pH 6.8) at the final concentration of 1.5% (w/w) have been selected as the most promising systems for further investigations, exploring the possibility of combinations to improve the rheological properties. Practical Application: Glucomannan, xanthan gum, tara gum, guar gum, konjac gum, and gellan gum have been chosen among the most common thickening agents derived from plants to perform a systematic investigation of the influence of pH, concentration, and temperature on the rheological properties of their water dispersions. The data obtained may be useful for further application of these hydrogels in the nutraceutical field as thickeners, texture modifiers, emulsifiers, stabilizers, and gelling agents. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract The investigation of colloidal properties of nanosystems represents a fundamental issue for the development of nanotechnology-based medicines. The aim of this study is to combine various techniques in order to characterize more comprehensively chimeric nanovesicles composed of block or gradient block copolymers with different architectures and compositions. Several chimeric systems were prepared and the impact of the block [poly(ε-caprolactone)−poly(ethylene oxide); PEO-b-PCL] and gradient block [poly(2-methyl-2-oxazoline)-grad-poly(2-phenyl-2-oxazoline); MPOx] copolymers on the physicochemical and morphological characteristics of conventional 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes was examined. Light scattering techniques and cryo-TEM were used for the physicochemical and morphological characterization of the prepared systems. The size and the morphology were strongly related to the architecture and the composition of the polymeric compounds. Micro differential scanning calorimetry and high-resolution ultrasound spectroscopy were used for investigating the interactions between the DPPC lipids and the polymeric guest. An increase in the main transition temperature was observed for the prepared chimeric systems in comparison to DPPC liposomes. In conclusion, a detailed characterization of the colloidal behavior of chimeric liposomes can benefit from the combination of the aforementioned techniques that operate synergistically, giving information on their physicochemical and morphological characteristics as well as on their thermotropic behavior. [ABSTRACT FROM AUTHOR]

The development of effective control strategies targeting non-native ambrosia beetles (Coleoptera: Curculionidae: Scolytinae and Platypodinae) represents an emerging challenge. This is due both to their rapid spread into climatically suitable newly invaded regions rich in susceptible host plants and to the limited knowledge concerning sustainable management tools. In this context, the use of botanical insecticides, such as plant essential oils (EOs), is considered a promising option in Integrated Pest Management (IPM) strategies as an alternative to conventional insecticides for sustainable crop protection. Here, the impact of five EO nanoemulsions (Rosmarinus officinalis L. cultivar verbenone, Carlina acaulis L., Laurus nobilis L., Cupressus sempervirens L., and Betula alba L.) on the choice behavior, host colonization and progeny production by the invasive ambrosia beetle Xylosandrus compactus (Eichhoff) was evaluated under laboratory and semi-field conditions. The chemical composition of tested EOs was firstly evaluated by means of gas chromatography-mass spectrometry (GC-MS) analyses. Then, EO nanoemulsions were prepared and characterized through dynamic light scattering (DLS). Tested EO nanoemulsions showed single or bimodal droplet size distributions in the nanometric range. Results highlighted a significant repellent activity of R. officinalis cv. verbenone and C. acaulis EO nanoemulsions (at 3% EO concentration). However, the trend for repellence of the R. officinalis EO against the beetle was not confirmed at decreasing EO concentrations (i.e., 1% and 0.5%). Nanoemulsions based on C. acaulis EO significantly affected the beetle choices regardless of the tested EO concentration. Indeed, in no choice bioassays, a significantly lower number of individuals started infesting stems treated with these nanoemulsions. On the other hand, no effect of the EO treatment was found on the number of offspring produced by survived beetle females. The repellence by R. officinalis and C. acaulis EOs was confirmed in semi-field conditions. Overall, our findings provide new insights toward the use of R. officinalis and C. acaulis EOs as repellents of X. compactus , suggesting their future incorporation in non-chemical strategies, such as 'push-pull', as part of sustainable IPM packages targeting this invasive pest. [Display omitted] • Little is known about the use of plant essential oils for managing Xylosandrus ambrosia beetles. • Essential oils of Rosmarinus officinalis cv verbenone and Carlina acaulis alter host colonization by Xylosandrus compactus. • Nanoemulsions based on Carlina acaulis EO repelled the beetle regardless of the tested EO concentration. [ABSTRACT FROM AUTHOR]

Chitosan is a biodegradable and biocompatible natural polysaccharide that has a wide range of applications in the field of pharmaceutics, biomedical, chemical, cosmetics, textile and food industry. One of the most interesting characteristics of chitosan is its antibacterial and antifungal activity, and together with its excellent safety profile in human, it has attracted considerable attention in various research disciplines. The antimicrobial activity of chitosan is dependent on a number of factors, including its molecular weight, degree of deacetylation, degree of substitution, physical form, as well as structural properties of the cell wall of the target microorganisms. While the sole use of chitosan may not be sufficient to produce an adequate antimicrobial effect to fulfil different purposes, the incorporation of this biopolymer with other active substances such as drugs, metals and natural compounds in nanosystems is a commonly employed strategy to enhance its antimicrobial potential. In this review, we aim to provide an overview on the different approaches that exploit the antimicrobial activity of chitosan-based nanosystems and their applications, and highlight the latest advances in this field. [ABSTRACT FROM AUTHOR]

Polymeric hydrogels are common dosage forms designed for the topical administration of antimicrobial drugs to treat vaginal infections. One of the major advantages of using chitosan in these formulations is related to the intrinsic and broad antimicrobial activity exerted on bacteria and fungi by this natural polymer. Most vaginal yeast infections are caused by the pathogenic fungus Candida albicans. However, despite the anti-Candida activity towards and strains susceptibility to low molecular weight chitosan being documented, no information is available regarding the antimicrobial efficacy of mixed hydrogels in which chitosan is dispersed in a polymeric matrix. Therefore, the aim of the study is to evaluate the anti-Candida activity against eight different albicans and non-albicans strains of a mixed hydroxypropyl methylcellulose (HPMC)/chitosan hydrogel. Importantly, chitosan was dispersed in HPMC matrix either assembled in nanoparticles or in a monomolecular state to eventually correlate any variation in terms of rheological and mucoadhesive properties, as well as anti-Candida activity, with the chitosan form. Hydrogels containing 1% w/w chitosan, either as free polymer chain or assembled in nanoparticles, showed an improved mucoadhesiveness and an anti-Candida effect against all tested albicans and non-albicans strains. Overall, the results demonstrate the feasibility of preparing HPMC/CS mixed hydrogels intended for the prevention and treatment of Candida infections after vaginal administration. [ABSTRACT FROM AUTHOR]

In this work, the profile of the volatile compounds has been determined for the first time in fresh donkey milk and in donkey milk subjected to accelerated shelf-life test, freeze-drying and spray-drying processes. The effects of freeze-drying and spray-drying processes in donkey milk have been analyzed also on three representative whey proteins, β-lactoglobulin, α-lactalbumin and lysozyme, by determining the total amount, the enzymatic activity and the thermal stability. Considering the volatile compounds in fresh donkey milk, 2-heptanone, 1,3-bis (1,1-dimethylethyl)-benzene, nonanal, d -limonene, octanoic acid, and 1-octanol were detected. The accelerated shelf-life test revealed a constant increase of octanoic acid, 2-heptanone, and nonanal compared to fresh donkey milk (P < 0.001) and the appearance of ethyl octanoate, ethyl dodecanoate, 2-nonanone and 2-undecanone, indicating that these compounds may be highly eligible markers of donkey milk shelf-life. Freeze-drying and spray-drying affected β-lactoglobulin and lysozyme content in donkey milk. In particular, spray-drying process decreased significantly lysozyme enzymatic activity (58% of residual activity) and β-lactoglobulin content (6.43 mg/mL in fresh milk vs 5.51 mg/mL in spry-dried milk) due to the high temperature to which donkey milk is subjected. [ABSTRACT FROM AUTHOR]

In this study, we evaluate the influence of zein aggregation in aqueous ethanol dispersions on the properties of zein films. The effects of zein concentration, ethanol content and temperature on transmittance of zein dispersions were investigated. Dynamic light scattering was used to measure the degree of zein aggregation in the dispersions. The results indicate that particle size of zein increased with higher zein concentration, lower ethanol level and at lower temperatures. Zein films were prepared by casting from 70% and 90% aqueous ethanol dispersions at different drying temperatures and were evaluated for appearance, thermomechanical and mechanical properties. Higher ethanol levels and higher drying temperatures promoted the formation of more homogenous films. Films made from higher ethanol dispersions had lower glass transition temperatures than those made from lower ethanol dispersions. Moreover, the fragility factor classified the films as strong systems. Mechanical properties of films were measured at different drying temperatures. Stiffer and more resistant films were developed as the drying temperature increased. In conclusion, film properties can be tailored by controlling the composition of the film casting solvent and the drying temperature. Differences in film properties were found to relate to differences in initial degree of aggregation of zein dispersions. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the relationship between controlled release behaviour, swelling and initial water sorption of zein powder filled into hard gelatin capsules. Release, release rate and dissolution efficiency of various physical mixtures of zein and propranolol HCl filled into capsules were measured by dissolution testing. As the gelatin shell dissolved, zein rapidly formed a matrix, providing prolonged drug release, after an initial drug burst. Drug loading and ionic strength of the medium significantly influenced drug release. Imaging and gravimetric analysis were used to investigate matrix swelling and erosion. Zein matrices swelled like hydrophilic matrices, yet were practically non-erodible. Moreover, a strong significant positive correlation was found between matrix swelling and drug release (Pearson's correlation coefficient, r ≥ 0.9657, p -value ≤ 0.0017), suggesting that the degree of swelling governed drug release. The tensiometry test revealed that the initial ingress of media through the pores of zein powder was significantly limited by a reduction of the capillary radii of these pores, as a result of rapid polymer hydration. In conclusion, the rapid hydration of zein powder could explain the matrix formation and the controlled release observed with the capsules in the dissolution studies. Initial hydration, swelling and release behaviour were dependent on the ionic strength of the medium. [ABSTRACT FROM AUTHOR]

Recently, plant secondary metabolites have been considered for developing new generation nematicides. Carlina acaulis L. (Asteraceae) contains an essential oil (EO) exhibiting significant insecticidal activity with limited impact on beneficial aquatic and terrestrial organisms. Herein, we report the development of a C. acaulis essential oil EO (CEO)-based nanoemulsion (CEONE) for managing the phytoparasitic nematode Meloidogyne incognita. Initially, pure C. acaulis essential oil EO (CEO) was evaluated for its toxicity against second stage juveniles (J2) of M. incognita as well as for the interruption of the nematode biological cycle into the roots of artificially inoculated tomato plants. CEO was analysed through gas chromatography-mass spectrometry (GC-MS) analysis. Therefore, CEONE was developed to ameliorate CEO efficacy, and physico-chemically characterized. GC-MS showed that the tested CEO was mainly composed by the polyacetylene carlina oxide (96%). CEO exhibited significant in vivo and in vitro activity against M. incognita. Of note, CEONE was more effective in controlling nematodes into tomato infested roots. Overall, the CEO could be practically exploited for a new class of nematicidal agents. [Display omitted] • Carlina acaulis essential oil EO (CEO)-based nanoemulsion (CEONE) controls Meloidogyne incognita. • CEO contains polyacetylene carlina oxide as the predominant component (96%). • CEO significant acts on M. incognita both in in vitro and in vivo experiments. • CEONE was more effective in controlling nematodes into tomato infested roots. • CEO could be practically exploited for a new class of nematicidal agents. [ABSTRACT FROM AUTHOR]

Carlina acaulis L., belonging to the Asteraceae (Compositae) family, is a perennial herb native to the Alps, which has a long history as a food and traditional remedy , being one of the most important medicinal plants in Europe. Its reported uses go from diuretic, cholagogic, and antibacterial agent for the treatment of gastritis, skin diseases, acne, eczema, and ulcers. Even if this plant presents a rich phytocomplex, its root essential oil (EO) is the product that surely raised most research interest. It has the exceptional feature of having as main constituent the polyacetylene carlina oxide, and is currently listed among botanicals employable in food supplements in Europe. This EO and carlina oxide showed an encouraging bioactivity on a variety of bacteria and fungi, such as Staphylococcus aureus , Escherichia coli , Klebsiella pneumoniae , Pseudomonas aeruginosa , Proteus vulgaris , Candida albicans and C. glabrata. Moreover, these products showed marked insecticidal and acaricidal activities against insect pests and vectors of medical, agricultural, and economic importance, revealing to be promising in the horizon of botanical insecticides and acaricides. Its EO as well as carlina oxide resulted to be active on vectors, e.g. Culex quinquefasciatus, urban and livestock pests e.g. Musca domestica , stored product pests e.g. Acarus siro , Trogoderma granarium and Prostephanus truncatus , and agricultural pests, e.g. Lobesia botrana , Bactrocera oleae and Ceratitis capitata, among others. These insecticidal properties are also accompanied by low-to-moderate toxicity on non-target organisms such as earthworms and aquatic microcrustaceans, as well as on vertebrate cells and mammals. Innovative formulations have been developed and tested for applying these products in real-world conditions with encouraging results. Different cultivation systems of C. acaulis have been carried out, with classic field cultivation having the greatest advantage over other systems, such as hydroponic and in vitro micropropagation in terms of insecticidal and acarcicidal compound yield. This review puts a focus for the first time on C. acaulis , its active compounds and its potential against vectors, pests, and pathogens, and on current issues related to its cultivation on a large-scale level. Moreover, its biological properties and related encapsulation techniques developed are extensively reviewed. [Display omitted] • Carlina acaulis potential as a green insecticide and acaricide was reviewed. • Carlina oxide was examined as the main responsible for the insecticidal action. • Non-target toxicity was investigated. • Challenges and perspectives for the plant cultivation were considered. • The crucial role of nanoformulations for essential oil delivery was discussed. [ABSTRACT FROM AUTHOR]

Smyrnium olusatrum L. is a horticultural crop cultivated during the Roman age for culinary and curative uses. The essential oil extracted from this plant (AEO) is rich in bioactive constituents such as isofuranodiene and germacrone. Several previous studies revealed that AEO and its isolated components possess interesting therapeutic features, such as antiproliferative, neuritogenic, hepatoprotective and antioxidant properties. Nevertheless, AEO has stability problems because of the high concentration of its main components. This issue makes AEO very difficult to handle and use. Thus, AEO was formulated as microemulsions known for their thermodynamic stability and easiness of preparation. AEO was hydrodistilled from inflorescences of S. olusatrum and its composition determined by different chromatographic methods. The microemulsions were developed using a central composite design and their activity tested using the MTT assay. The present study demonstrated the possibility to formulate stable AEOmicroemulsionswhere the crystallization of isofuranodiene is avoided, and the AEO biological activity is maintained. [ABSTRACT FROM AUTHOR]

Food safety is a fundamental concern for both consumers and the food industry, especially as the numbers of reported cases of food-associated infections continue to increase. Industrial surfaces can provide a suitable substrate for the development and persistence of bacterial organized in biofilms that represent a potential source of food contamination. The negative consumer perception of chemical disinfectants has shifted the attention to natural substances, such as plant extracts. The aim of this study was to investigate the possibility of using the essential oils (EOs) in the fight against S . aureus biofilms. First, the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Minimum Biofilm Inhibitory Concentration (MBIC), Minimum Biofilm Eradication Concentration (MBEC) of eleven EOs against S . aureus were determined. Cinnamomum cassia and Salvia officinalis EOs showed the greatest antibacterial properties with 1.25% MIC and MBC, 1.25% MBIC and 2.5% MBEC respectively. Gas Chromatography/Mass Spectrometry analysis revealed cinnamaldehyde (82.66%) and methoxy cinnamaldehyde (10.12%) as the most abundant substances of C . cassia , while cis-thujone (23.90%), camphor (19.22%) and 1.8-cineole (10.62%) of S . officinalis . Three different microemulsions, formulated with C . cassia , S . officinalis or both, were finally tested against S . aureus biofilms in different culture media and growth conditions, causing a > 3 logarithmic reductions in S . aureus 24 h-old biofilms and desiccated biofilms, and up to 68% of biofilm removal after 90 min of exposure. The obtained data suggest the potential use of EOs, alone or in combination, for the formulation of sanitizers as alternative or in support in the disinfection of contaminated surfaces. [ABSTRACT FROM AUTHOR]

[Display omitted] The abilities of sub-cellular targeting and stimuli-responsiveness are critical challenges in pharmaceutical nanotechnology. In the present study, glyceryl monooleate (GMO)-based non-lamellar lyotropic liquid crystalline nanoparticles were stabilized by the poly(2-(dimethylamino)ethyl methacrylate)- b -poly(lauryl methacrylate) block copolymer carrying tri-phenyl-phosphine cations (TPP-QPDMAEMA- b -PLMA), either used alone or in combination with other polymers as co-stabilizers. The systems were designed to perform simultaneously sub-cellular targeting, stimuli-responsiveness and to exhibit stealthiness. The physicochemical characteristics and fractal dimensions of the resultant nanosystems were obtained from light scattering techniques, while their micropolarity and microfluidity from fluorescence spectroscopy. Their morphology was assessed by cryo-TEM, while their thermal behavior by microcalorimetry and high-resolution ultrasound spectroscopy. The analyzed properties, including the responsiveness to pH and temperature, were found to be dependent on the combination of the polymeric stabilizers. The subcellular localization was monitored by confocal microscopy, revealing targeting to lysosomes. Subsequently, resveratrol was loaded into the nanosystems, the entrapment efficiency was investigated and in vitro release studies were carried out at different conditions, in which a stimuli-triggered drug release profile was achieved. In conclusion, the proposed multi-functional nanosystems can be considered as potentially stealth, stimuli-responsive drug delivery nanocarriers, with targeting ability to lysosomes and presenting a stimuli-triggered drug release profile. [ABSTRACT FROM AUTHOR]

Toxicity is one of the main concerns limiting the use of surfactants. Many efforts have been devoted to the development of new amphiphilic molecules characterized by a lower toxicological profile and environmental impact. N -acyl amino acids are a class of anionic surfactants that can find applications in different technological fields as an alternative to sulphate-based surfactants (e.g., sodium dodecyl sulphate). The understanding of the relationship between chemical structure and toxicological profile is fundamental for the disclosure of the full potential of these amphiphiles. With this aim, two series of N -acyl surfactants, with different length of the hydrophobic tails and serine or alanine as polar head, were synthesized and fully characterized. The correlation between the surface and toxicological parameters allowed highlighting the role exerted by the length of the hydrocarbon chain and the polar head on cytotoxicity. The length of the hydrocarbon chain mainly influences surface properties and toxicological parameters, while the amino acid polar head may play a key role only on cellular toxicity. Overall, our data suggest that minor differences in the polar head, not significantly affecting CMC values, may have an impact on cytotoxicity. [ABSTRACT FROM AUTHOR]

This study focuses on the evaluation of microfoam produced from processed dairy milk using the steaming function of the espresso machine as a function of temperature (30–80 °C), milk type (pasteurised or UHT), and whey protein contents. Foam characteristics, i.e., foam stability, viscosity, bubble size distribution noticeably varied depending on milk processing type and steam heating temperature. Foams made from pasteurised whole milk tended to be more stable. Bubbles in pasteurised milk foam were better distributed, especially at the temperature of 60 °C. It was observed that the optimal final temperature of steam frothing was in the range of 50 °C–60 °C. The results of sensory tests showed that consumers differentiated between the aroma and flavour of pasteurised and UHT milk, describing the degree of this difference from moderate to strong. [ABSTRACT FROM AUTHOR]

The essential oils (EOs) produced by a number of Apiaceae species are well known for their insecticidal efficacy against a wide spectrum of insects, including vectors, stored product and agricultural pests. In the real world, rawly formulated EOs are scarcely effective due to their low chemical stability, limited persistence into the environment, and poor hydrophilicity. Therefore, for practical applications they need to be encapsulated using nanocarriers. In the present study, we evaluated two novel EO-based nanoemulsions (NEs) derived from Pimpinella anisum and Trachyspermun ammi , two plants with documented insecticidal effectiveness, for the management of stored product insects causing economic damages, including Tribolium castaneum , Tribolium confusum , Tenebrio molitor , Trogoderma granarium adults or larvae, and Acarus siro adults or nymphs. The NEs were prepared by a high-pressure homogenization procedure and determined according to the distribution of particle size through dynamic light scattering. Pimpinella anisum EO resulted mainly dominated by the phenylpropanoid (E)-anethole, while T. ammi EO was mainly composed of thymol, p -cymene, and γ -terpinene. Each EO-based NE was tested at two concentrations (500 and 1000 ppm) on stored wheat. We evaluated mortality values of the arthropod pests after 4 h, 8 h, and 16 h, and daily from 1 to 7 days. Complete mortality was achieved for T. castaneum larvae on wheat sprayed with 1000 ppm of 4% (w/w) P. anisum EO-based NE after 6 days of exposure. Similarly, the 8% (w/w) T. ammi EO-based NE killed 100.0% of the tested T. confusum larvae after 7 days to 1000 ppm. When A. siro adults were exposed to 1000 ppm of the 8% (w/w) T. ammi EO-based NE, 89.4% of the tested individuals were killed after 7 days. Binary EO-based NE combination toxicity tests were also carried out. Almost all T. molitor adults (97.8%) died after 7 days to 1000 ppm of 3% (w/w) T. ammi + 3% (w/w) P. anisum EO-based NE. The 3% (w/w) T. ammi + 3% (w/w) P. anisum EO-based NE killed 98.6% of T. granarium adults after 7 days at 1000 ppm. Overall, the tested Apiaceae EO-based NEs exhibited relevant pesticidal efficacy under short exposure intervals, therefore they could be taken into account as auxiliary management tools towards the sustainable protection of durable commodities in storages. [Display omitted] • 4% (w/w) P. anisum EO-based NE killed all T. castaneum larvae after 6 days at 1000 ppm. • 8% (w/w) T. ammi EO-based NE killed all T. confusum larvae after 7 days at 1000 ppm. • 3% (w/w) T. ammi + 3% (w/w) P. anisum EO-based NE killed 97.8% T. molitor adults after 7 days at 1000 ppm. • 3% (w/w) T. ammi + 3% (w/w) P. anisum EO-based NE killed 98.6% T. granarium adults after 7 days at 1000 ppm. [ABSTRACT FROM AUTHOR]

N -acyl amino acids-based surfactants are an attractive class of anionic amphiphiles alternative to sulphate-based surfactants, potentially employed as excipients for pharmaceutical applications in which an anionic surfactant is needed. Thus, a systematic characterization of their toxicological profile is required, particularly in comparison to sodium dodecyl sulphate (SDS), a widely employed surfactant in pharmaceutical formulations. This work reported a systematic study on the relationship between the structures of N -acyl amino acids-based surfactants, their physicochemical properties and toxicological profiles. N -Decanoyl aminoacids with different polar heads (leucine, methionine, serine and proline) were synthesized and characterized in terms of surface tension and aggregation properties. Different human cell lines (Caco-2, A549, Calu-3) and erythrocytes were selected as model for oral, respiratory or parenteral administration to evaluate surfactants cytotoxicity. Moreover, the ability of surfactants to interact with cell membranes was assessed by the Trans Epithelial Electrical Resistance (TEER). Results suggested that the different polar heads affect the aggregation state and cell toxicity profiles of surfactants, but not their surface properties. According to the toxicity assays, all N -decanoyl surfactants were less toxic than SDS, suggesting that hydrophilic interactions between amphiphiles and cell membranes play a key role in determining cellular toxicity. [ABSTRACT FROM AUTHOR]