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Despite the appealing properties of random copolymers, the use of these biomaterials in association with phospholipids is still limited, as several aspects of their performance have not been investigated. The aim of this work is the formulation of lipid/random copolymer platforms and the comprehensive study of their features by multiple advanced characterization techniques. Both biomaterials are amphiphilic, including two phospholipids (1,2-dioctadecanoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)) and a statistical copolymer of oligo (ethylene glycol) methyl ether methacrylate (OEGMA) and 2-(diisopropylamino) ethyl methacrylate (DIPAEMA). We examined the design parameters, including the lipid composition, the % comonomer ratio, and the lipid-to-polymer ratio that could be critical for their behavior. The structures were also probed in different conditions. To the best of the authors’ knowledge, this is the first time that P(OEGMA-co-DIPAEMA)/lipid hybrid colloidal dispersions have been investigated from a membrane mechanics, biophysical, and morphological perspective. Among other parameters, the copolymer architecture and the hydrophilic to hydrophobic balance are deemed fundamental parameters for the biomaterial co-assembly, having an impact on the membrane’s fluidity, morphology, and thermodynamics. Exploiting their unique characteristics, the most promising candidates were utilized for methotrexate (MTX) loading to explore their encapsulation capability and potential antitumor efficacy in vitro in various cell lines.

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.

Background: Compounding solid oral dosage forms into liquid preparations is a common practice for administering drug therapy to patients with swallowing difficulties. This is particularly relevant for those on enteral nutrition, where factors such as the administration procedure and co-administration of enteral nutrition play crucial roles in effective drug delivery. Due to the limited studies focused on this practice, the impact of co-administered nutrition remains unclear. Methods: Pravastatin tablets were compounded into two liquid formulations and administered through three independent tubes for ten cycles. The drug amount was quantified upstream and downstream of the tubes both with and without different (fiber content) nutritional boluses. Results: The compounding procedure did not lower the drug amount with respect to the original tablets. However, when the liquid formulation was pumped through the tubes, a statistically significant reduction in the pravastatin administered (between 4.6% and 11.3%) was observed. The co-administration of different nutritional boluses or the compounding procedure did not affect the general results. Conclusions: Pravastatin loss appears unavoidable when administered via the enteral tube. Although, in this case, the loss was of limited clinical relevance, it is important not to underestimate this phenomenon, especially with drugs having a narrow therapeutic index.

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.

Alopecia is a pathological and multifactorial condition characterised by an altered hair growth cycle and ascribed to different pathogenic causes. Cell energetic imbalances in hair follicles occurring in this disorder could lead to the production of some “metabolic wastes”, including squalene and lactic acid, which could be involved in the clinically observed sheath damage. The aim of this work was the extraction and analytical quantification of squalene and lactic acid from hair bulbs of subjects with clinical alopecia in comparison with controls, using HPLC-DAD and HPLC-MS techniques. The analytical quantification was performed after a preliminary observation through a polarised optical microscope to assess sheath damage and morphological alterations in the cases group. A significantly larger amount of squalene was quantified only in subjects affected by alopecia (n = 31) and with evident damage to hair sheaths. For lactic acid, no statistically significant differences were found between cases (n = 21) and controls (n = 21) under the experimental conditions used. Therefore, the obtained results suggest that squalene can represent a metabolic and a pathogenic marker for some alopecia conditions.

The development of functional foods in the dairy sector represents a flourishing field of technological research. In this study, an Italian fresh cheese as “giuncata” was enriched with inulin, a dietary fiber, with the aim of developing a product with improved nutritional properties in terms of prebiotic action on intestinal microbiota. An inulin concentration of ~4% w/w was determined in the fresh cheese after the fortification process, enabling the claim of being a “source of dietary fiber” (inulin > 3 g/100 g) according to the European regulation. The addition of inulin has no effect on the pH of cheese and does not relevantly influence its color as well as the total fat content (fat reduction ~0.61%) in comparison to the control. Mechanical properties of the cheese were also not markedly affected as evidenced from rheological and tensile testing analyses. Indeed, the incorporation of inulin in “giuncata” only exerts a slight “softening effect” resulting in a slightly lower consistency and mechanical resistance in comparison to the control. Overall, this study demonstrates the feasibility of producing a fiber-enriched dairy functional food from a large consumed fresh and soft cheese as “giuncata”.

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.

Essential oil (EO)-based nanoemulsions (NEs) are promising grain protectants in the management of stored-product pests. However, the potential impact of the stored-grain species on the green insecticide effectiveness has been poorly studied. In this study, two concentrations of EO-based NEs from Carlina acaulis L., Mentha longifolia (L.) Huds., and Hazomalania voyronii (Jum.) Capuron were evaluated as insecticides against the major stored-product pest Sitophilus oryzae (L.) on barley, oats, and maize kernels. The C. acaulis EO-based NE applied at 1000 ppm on barley achieved the highest mortality, killing 94.4% of S. oryzae adults after a 7-day exposure, followed by 1000 ppm of H. voyronii EO-based NE (83.3%). The lowest mortality (1.1%) was recorded with 500 ppm of M. longifolia EO-based NE on maize after the same interval. All tested NEs exhibited elevated efficacy when applied on barley, while mortalities were lower on oats and maize. Furthermore, C. acaulis EO-based NE was the most effective when applied on all commodities, followed by H. voyronii and M. longifolia EO-based NEs. Overall, our results highlighted the significant impact of the stored cereal on the insecticidal effectiveness of EO-based NE used for stored-product pest control. Sitophilus oryzae adults on barley can be adequately controlled through the application of C. acaulis and H. voyronii EO-based NEs.

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.

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.

New hydrophobic derivatives of cinnamic and hydroxycinnamic (ferulic and cumaric) acids obtained by chemical esterification of the carboxylic group with C10 linear alcohol were studied to evaluate their antioxidant capacity toward the superoxide anion and hydrogen peroxide in physiological buffer and in extra-virgin olive oil (EVO) or Nigella sativa oils. Results showed that cumaric and ferulic acids have higher antioxidants activity against superoxide anion and hydrogen peroxide than the other compounds. Cumaric acid and its C10-ester derivative were selected to be incorporated into EVO or Nigella sativa oil-based emulsions. The prepared emulsions had a comparable particle size distribution (in the range of 3–4 µm) and physical stability at least up to three months. Nigella sativa oil-based emulsions loaded with cumaric acid or its C10-ester showed a higher capacity to scavenger superoxide anion and hydrogen peroxide than EVO oil-based emulsions. In conclusion, cumaric acid or its C10-ester could promote the antioxidant properties of Nigella sativa oil when formulated as emulsions.

This study aimed to investigate the susceptibility of Trypanosoma brucei to the Anthriscus nemorosa essential oils (EOs), isolated compounds from these oils, and artificial mixtures of the isolated compounds in their conventional and nanoencapsulated forms. The chemical composition of the essential oils from the aerial parts and roots of Anthriscus nemorosa, obtained from a wild population growing in central Italy, were analyzed by gas chromatography/mass spectrometry (GC/MS). In both cases, the predominant class of compounds was monoterpene hydrocarbons, which were more abundant in the EOs from the roots (81.5%) than the aerial parts (74.0%). The overall results of this work have shed light on the biological properties of A. nemorosa EO from aerial parts (EC50 = 1.17 μg/mL), farnesene (EC50 = 0.84 μg/mL), and artificial mixtures (Mix 3–5, EC50 in the range of 1.27 to 1.58 μg/mL) as relevant sources of antiprotozoal substances. Furthermore, the pool measurements of ADP (adenosine diphosphate) and NTPs (nucleoside triphosphates) in the cultivated bloodstream form of trypanosomes exposed to different concentrations of EOs showed a disturbed energy metabolism, as indicated by increased pools of ADP in comparison to ATP (adenosine triphosphate) and other NTPs. Ultimately, this study highlights the significant efficacy of A. nemorosa EO to develop long-lasting and effective antiprotozoal formulations, including nanoemulsions.

Plants are considered to be an excellent source of new compounds with antibiotic activity. Carlina acaulis L. is a medicinal plant whose essential oil (EO) is mainly characterized by the polyacetylene carlina oxide, which has antimicrobial properties. The aim of this study was to evaluate the antimicrobial and antifungal activities of C. acaulis EO, carlina oxide, and nanoemulsion (NE) containing the EO. The EO was obtained through plant roots hydrodistillation, and carlina oxide was purified from it through silica gel column chromatography. The NE containing C. acaulis EO was prepared with the high-pressure homogenization method, and the minimum inhibitory concentration (MIC) was determined against several bacterial and fungal strains for all the C. acaulis-derived products. The latter resulted active versus all the screened Gram-positive bacterial strains and also on all the fungal strains with low MIC values. For yeast, the EO and carlina oxide showed good MIC values. The EO-NE demonstrated a better activity than the pure EO on all the tested bacterial and fungal strains. The results suggest that C. acaulis-derived products could be potential candidates for the development of natural antibacterial and antifungal agents.

Three-dimensional (3D) printing, or additive manufacturing, is a group of innovative technologies that are increasingly employed for the production of 3D objects in different fields, including pharmaceutics, engineering, agri-food and medicines. The most processed materials by 3D printing techniques (e.g., fused deposition modelling, FDM; selective laser sintering, SLS; stereolithography, SLA) are polymeric materials since they offer chemical resistance, are low cost and have easy processability. However, one main drawback of using these materials alone (e.g., polylactic acid, PLA) in the manufacturing process is related to the poor mechanical and tensile properties of the final product. To overcome these limitations, fillers can be added to the polymeric matrix during the manufacturing to act as reinforcing agents. These include inorganic or organic materials such as glass, carbon fibers, silicon, ceramic or metals. One emerging approach is the employment of natural polymers (polysaccharides and proteins) as reinforcing agents, which are extracted from plants or obtained from biomasses or agricultural/industrial wastes. The advantages of using these natural materials as fillers for 3D printing are related to their availability together with the possibility of producing printed specimens with a smaller environmental impact and higher biodegradability. Therefore, they represent a “green option” for 3D printing processing, and many studies have been published in the last year to evaluate their ability to improve the mechanical properties of 3D printed objects. The present review provides an overview of the recent literature regarding natural polymers as reinforcing agents for 3D printing.

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization.

Most insecticides commonly used in storage facilities are synthetic, an issue that generates concerns about food safety and public health. Therefore, the development of eco-friendly pest management tools is urgently needed. In the present study, a 6% (w/w) Hazomalania voyronii essential oil-based nanoemulsion (HvNE) was developed and evaluated for managing Tribolium confusum, T. castaneum, and Tenebrio molitor, as an eco-friendly wheat protectant. Larval and adult mortality was evaluated after 4, 8, and 16 h, and 1, 2, 3, 4, 5, 6, and 7 days, testing two HvNE concentrations (500 ppm and 1000 ppm). T. confusum and T. castaneum adults and T. molitor larvae were tolerant to both concentrations of the HvNE, reaching 13.0%, 18.7%, and 10.3% mortality, respectively, at 1000 ppm after 7 days of exposure. However, testing HvNE at 1000 ppm, the mortality of T. confusum and T. castaneum larvae and T. molitor adults 7 days post-exposure reached 92.1%, 97.4%, and 100.0%, respectively. Overall, the HvNE can be considered as an effective adulticide or larvicide, depending on the target species. Our results highlight the potential of H. voyronii essential oil for developing green nanoinsecticides to be used in real-world conditions against key stored-product pests.

Flavours and fragrances are volatile compounds of large interest for different applications. Due to their high tendency of evaporation and, in most cases, poor chemical stability, these compounds need to be encapsulated for handling and industrial processing. Encapsulation, indeed, resulted in being effective at overcoming the main concerns related to volatile compound manipulation, and several industrial products contain flavours and fragrances in an encapsulated form for the final usage of customers. Although several organic or inorganic materials have been investigated for the production of coated micro- or nanosystems intended for the encapsulation of fragrances and flavours, polymeric coating, leading to the formation of micro- or nanocapsules with a core-shell architecture, as well as a molecular inclusion complexation with cyclodextrins, are still the most used. The present review aims to summarise the recent literature about the encapsulation of fragrances and flavours into polymeric micro- or nanocapsules or inclusion complexes with cyclodextrins, with a focus on methods for micro/nanoencapsulation and applications in the different technological fields, including the textile, cosmetic, food and paper industries.

Platelet-rich plasma (PRP) is a nontransfusional hemocomponent, considered as a powerful concentrate of growth factors (GFs) therapeutically used to stimulate tissue regeneration. The use of autologous PRP, as the patient’s own biological material, for therapeutic purposes represents a safe and effective alternative to conventional treatments in both human and veterinary medicine. The aim of this study was the characterization of canine PRP from rheological and biological points of view. Thus, a characterization of the viscoelastic properties of the PRP systems was performed in order to clarify the influence of different calcium concentrations, in the presence of autologous thrombin-rich solution, on the PRP gels’ mechanical properties, from which the applicability of these systems in biomedical treatments is strongly dependent. Then, an evaluation of the content of GFs in PRP, activated or not with thrombin, and stored at different temperatures (37 °C and −20 °C) was performed over time, outlining, for the first time, the importance of the effect of physiological temperature (37 °C) on the production of GFs. A clinical case study conducted in a dog with a complete rupture of the common calcaneal tendon (Achilles tendon) confirmed the relevance of this hemocomponent in the daily veterinary clinical activity and the potential translational value for human health.

The growing interest in the development of green pest management strategies is leading to the exploitation of essential oils (EOs) as promising botanical pesticides. In this respect, nanotechnology could efficiently support the use of EOs through their encapsulation into stable nanoformulations, such as nanoemulsions (NEs), to improve their stability and efficacy. This technology assures the improvement of the chemical stability, hydrophilicity, and environmental persistence of EOs, giving an added value for the fabrication of natural insecticides effective against a wide spectrum of insect vectors and pests of public and agronomical importance. Carlina acaulis (Asteraceae) root EO has been recently proposed as a promising ingredient of a new generation of botanical insecticides. In the present study, a highly stable C. acaulis-based NE was developed. Interestingly, such a nanosystem was able to encapsulate 6% (w/w) of C. acaulis EO, showing a mean diameter of around 140 nm and a SOR (surfactant-to-oil ratio) of 0.6. Its stability was evaluated in a storage period of six months and corroborated by an accelerated stability study. Therefore, the C. acaulis EO and C. acaulis-based NE were evaluated for their toxicity against 1st instar larvae of the European grapevine moth (EGVM), Lobesia botrana (Denis & Schiffermüller, 1775) (Lepidoptera: Tortricidae), a major vineyard pest. The chemical composition of C. acaulis EO was investigated by gas chromatography–mass spectrometry (GC–MS) revealing carlina oxide, a polyacetylene, as the main constituent. In toxicity assays, both the C. acaulis EO and the C. acaulis-based NE were highly toxic to L. botrana larvae, with LC50 values of 7.299 and 9.044 µL/mL for C. acaulis EO and NE, respectively. The C. acaulis-based NE represents a promising option to develop highly stable botanical insecticides for pest management. To date, this study represents the first evidence about the insecticidal toxicity of EOs and EO-based NEs against this major grapevine pest.

Among the various innovative products obtainable from hemp (Cannabis sativa L.) waste biomass originating from different industrial processes, the essential oil (EO) deserves special attention in order to understand its possible application in different fields, such as cosmetics, pharmaceuticals, and botanical insecticides. For the purpose, in the present work, we studied the chemical composition of EOs obtained from different hemp varieties, namely Felina 32 and Carmagnola Selezionata (CS) using monoecious, male, and female inflorescences, and we evaluated their mosquitocidal activities on larvae and pupae of two main malaria vectors, Anopheles gambiae and An. stephensi. Then, in order to evaluate the safe use of hemp EOs for operators, the potential pro- or anti-inflammatory effect of hemp EOs together with their toxicological profile were determined on dermal fibroblasts and keratinocytes. Given the promising results obtained by insecticidal and anti-inflammatory studies, a preliminary evaluation of EOs encapsulation into nanoemulsions (NEs) has been performed with the aim to develop a formulation able to improve their poor physicochemical stability. Felina 32 and CS inflorescences provided EOs with an interesting chemical profile, with monoterpene and sesquiterpene hydrocarbons as the major components. This study highlighted the potential application of male inflorescences, which are usually discharged during hemp product processing. These EOs could be exploited as potential sustainable and eco-friendly insecticides, given their capability to be toxic against mosquitoes and the possibility to use them to prepare stable and safe formulations. The LC50 values found in this study (

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.

A method for the aqueous synthesis of stable and biocompatible citrate-coated palladium nanoparticles (PdNPs) in the size range comparable to natural enzymes (4−8 nm) has been developed. The toxicological profile of PdNPs was assessed by different assays on several cell lines demonstrating their safety in vitro also at high particle concentrations. To elucidate their cellular fate upon uptake, the localization of PdNPs was analyzed by Transmission Electron Microscopy (TEM). Moreover, crucial information about their intracellular stability and oxidation state was obtained by Sputtering-Enabled Intracellular X-ray Photoelectron Spectroscopy (SEI-XPS). TEM/XPS results showed significant stability of PdNPs in the cellular environment, an important feature for their biocompatibility and potential for biomedical applications. On the catalytic side, these PdNPs exhibited strong and broad antioxidant activities, being able to mimic the three main antioxidant cellular enzymes, i.e., peroxidase, catalase, and superoxide dismutase. Remarkably, using an experimental model of a human oxidative stress-related disease, we demonstrated the effectiveness of PdNPs as antioxidant nanozymes within the cellular environment, showing that they are able to completely re-establish the physiological Reactive Oxygen Species (ROS) levels in highly compromised intracellular redox conditions.

The management of parasites, insect pests and vectors requests development of novel, effective and eco-friendly tools. The development of resistance towards many drugs and pesticides pushed scientists to look for novel bioactive compounds endowed with multiple modes of action, and with no risk to human health and environment. Several natural products are used as alternative/complementary approaches to manage parasites, insect pests and vectors due to their high efficacy and often limited non-target toxicity. Their encapsulation into nanosystems helps overcome some hurdles related to their physicochemical properties, for instance limited stability and handling, enhancing the overall efficacy. Among different nanosystems, micro- and nanoemulsions are easy-to-use systems in terms of preparation and industrial scale-up. Different reports support their efficacy against parasites of medical importance, including Leishmania, Plasmodium and Trypanosoma as well as agricultural and stored product insect pests and vectors of human diseases, such as Aedes and Culex mosquitoes. Overall, micro- and nanoemulsions are valid options for developing promising eco-friendly tools in pest and vector management, pending proper field validation. Future research on the improvement of technical aspects as well as chronic toxicity experiments on non-target species is needed.

Quaternary ammonium amphiphiles are a class of compounds with a wide range of commercial and industrial uses. In the pharmaceutical field, the most common quaternary ammonium surfactant is benzalkonium chloride (BAC), which is employed as a preservative in several topical formulations for ocular, skin, or nasal application. Despite the broad antimicrobial activity against Gram-positive and Gram-negative bacteria, as well as fungi and small enveloped viruses, safety concerns regarding its irritant and cytotoxic effect on epithelial cells still remain. In this work, quaternary ammonium derivatives of leucine esters (C10, C12 and C14) were synthesised as BAC analogues. These cationic surfactants were characterised in terms of critical micelle concentration (CMC, by tensiometry), cytotoxicity (MTS and LDH assays on the Caco-2 and Calu-3 cell lines) and antimicrobial activity on the bacterial species Staphylococcus aureus and Enterococcus faecalis among the Gram-positives, Escherichia coli and Pseudomonas aeruginosa among the Gram-negatives and the yeast Candida albicans. They showed satisfactory surface-active properties, and a cytotoxic effect that was dependent on the length of the hydrophobic chain. Lower minimum inhibiting concentration (MIC) values were calculated for C14-derivatives, which were comparable to those calculated for BAC toward Gram-positive bacteria and slightly higher for Gram-negative bacteria and C. albicans. Thus, the synthesised leucine-based quaternary ammonium cationic surfactants can potentially find application as promising surface-active compounds with antimicrobial activity.

Pharmaceutical formulations suitable for dysphagic patients are not always commercially available, motivating caregivers to crush tablets or open capsules to facilitate swallowing. Since this action may modify the characteristics of the medicine, it should be considered potentially inappropriate. This paper is the first to focus on how hospitalization affected the rate of potentially inappropriate prescriptions (PIPs) and the incidence of dosage form-related PIPs in elderly patients with dysphagia. Data was collected by reviewing patient medical records in the Italian National Research Center on Aging of Ancona. The therapy at admission and discharge was analysed in terms of: inappropriate drug associations, inappropriate drugs for dysphagic patients, inappropriate dosage forms and inappropriate dosage form modifications. Forty-one dysphagic patients with an average age of 88.3 years were included in the study and 451 prescriptions were analysed. PIPs were widespread at admission, and hospitalization did not improve the situation in a statistically significant manner. The most common PIPs identified (>80%) were related to dosage form selection and modification. This study highlights a clear need for continuing medical education about prescription appropriateness and modification of solid dosage forms in patients with dysphagia.

Self-assembling block copolymers (poloxamers, PEG/PLA and PEG/PLGA diblock and triblock copolymers, PEG/polycaprolactone, polyether modified poly(Acrylic Acid)) with large solubility difference between hydrophilic and hydrophobic moieties have the property of forming temperature dependent micellar aggregates and, after a further temperature increase, of gellifying due to micelle aggregation or packing. This property enables drugs to be mixed in the sol state at room temperature then the solution can be injected into a target tissue, forming a gel depot in-situ at body temperature with the goal of providing drug release control. The presence of micellar structures that give rise to thermoreversible gels, characterized by low toxicity and mucomimetic properties, makes this delivery system capable of solubilizing water-insoluble or poorly soluble drugs and of protecting labile molecules such as proteins and peptide drugs.

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.