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Reflectance spectroscopy has emerged as a powerful analytical technique in the field of dermatology, offering a non-invasive strategy to assess several cutaneous properties and skin response to topical products. By analyzing reflected light across different wavelengths, reflectance spectroscopy allows the quantification of cutaneous parameters, such as erythema index and melanin content. Moreover, this analytical technique enables the monitoring of any changes in skin physiology facilitating the assessment of long-term effects of topical products as well as predicting cutaneous diseases. This review provides an overview of the application of reflectance spectroscopy in investigating skin properties and reaction to topical applied products, including both pharmaceutical and cosmetic formulations, thereby aiding in the development of personalized solutions tailored to individual needs.

The cosmetics industry has experienced rapid growth, driven by consumer demand for products in line with modern lifestyles and technological advances, with greater awareness of the impacts on health and the ecosystem. This review explores the potential use of antibacterial compounds derived from food waste as sustainable alternatives to synthetic preservatives in cosmetic products. Waste obtained from food, including fruit peels, seeds, and plant remnants, is rich in natural bioactives, including polyphenolic compounds and essential oils that exhibit antimicrobial, antioxidant, anti-inflammatory, and soothing features. The integration of these natural ingredients not only improves the shelf-life and safety of cosmetics but also promotes environmentally friendly practices. We discuss the sources and antimicrobial efficacy of these compounds, along with recent technological innovations. This sustainable approach responds to consumer preferences for natural ingredients, reduces food waste, and supports environmental sustainability, ultimately increasing the value and attractiveness of cosmetic products.

Abstract The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid crystals are proposed as a new ophthalmic drug delivery system. Acyclovir was chosen as model drug for its solubility and its controlled release from cubic phase was achieved. We demonstrated the effortless application of lamellar phase on corneal surface and its ability to convert itself in cubic phase in situ. While the complex viscosity of lamellar phase was affected by temperature (5.1 ± 1.4 kPa·s at 25 °C and 0.12 ± 0.001 Pa·s at 35 °C, respectively), the cubic phase shown no changes in viscosity values and shear thinning behaviour at both temperatures and even in presence of the drug The degradation kinetic of drug-loaded cubic phase was slightly slower than the empty formulation, recording 27.92 ± 1.43% and 33.30 ± 3.11% of weight loss after 8 h. Ex vivo studies conducted on porcine eyeballs and isolated cornea confirmed the instantaneous transition to cubic phase, its ability to resist to gravity force, and forced dripping of simulated tear fluid. Histopathological investigation showed how treated cornea did not report changes in epithelial and stroma structures. In summary, lyotropic liquid crystals could represent an advantageous ophthalmic drug delivery system.

Resource depletion and food waste accumulation represent a tremendous socio-economic and environmental problem. One promising strategy involves the use of byproducts derived from food waste as ingredients for cosmetic products. The aim of this work is to propose clementine peels and olive leaf extracts as value-added bioproducts for a cosmetic cream. Extracts were obtained by super critical extraction showing an antioxidant activity of ca. 25%. No cytotoxic effects of the extracts were recorded on keratinocyte cells up to a concentration of 4% v/v ratio within 24 h. The incorporation of clementine peels and olive leaf extracts into creams did not compromise their stability, as demonstrated by Turbiscan analyses at room and extreme (40 °C) storage conditions. The safety profiles of the final cosmetic formulations were further in vivo demonstrated on human volunteers. We analyzed the trans-epidermal water loss and variation of the skin’s erythematous index, which showed profiles that almost overlapped with the negative control. Moreover, rheological analysis of the resulting creams evidences their suitable spreadability with similar pseudoplastic profiles, although a slight reduction of viscosity was recorded by improving the extracts’ concentrations. The proposed approach highlights the advantage of combining byproduct resources and supercritical fluid extraction to obtain a safe and eco-friendly face cream.

Chimeric Antigen Receptor (CAR)-modified T lymphocytes represent one of the most innovative and promising approaches to treating hematologic malignancies. CAR-T cell therapy is currently being used for the treatment of relapsed/refractory (r/r) B-cell malignancies including Acute Lymphoblastic Leukemia, Large B-Cell Lymphoma, Follicular Lymphoma, Multiple Myeloma and Mantle Cell Lymphoma. Despite the unprecedented clinical success, one of the major issues of the approved CAR-T cell therapy – tisagenlecleucel, axicabtagene, lisocabtagene, idecabtagene, ciltacabtagene and brexucabtagene – is the uncertainty about its persistence which in turn could lead to weak or no response to therapy with malignancy recurrence. Here we show that the prognosis of patients who do not respond to CAR-T cell therapy is still an unmet medical need. We performed a systematic review and meta-analysis collecting individual data on Duration of Response from at least 12-month follow-up studies. We found that the pooled prevalence of relapse within the first 12 months after CAR-T infusion was 61% (95% CI, 43%−78%); moreover, one year after the infusion, the analysis highlighted a pooled prevalence of relapse of 24% (95% CI, 11%−42%). Our results suggest that identifying potential predictive biomarkers of response to CAR-T therapy, especially for patients affected by the advanced stage of blood malignancies, could lead to stratification of the eligible population to that therapy, recognizing which patients will benefit and which will not, helping regulators to make decision in that way.

As many natural origin antioxidants, resveratrol is characterized by non-suitable physicochemical properties for its topical application. To allow its benefits to manifest on human skin, resveratrol has been entrapped within liquid crystal nanocarriers (LCNs) made up of glyceryl monooleate, a penetration enhancer, and DSPE-PEG 750. The nanosystems have been more deeply characterized by using dynamic light scattering and Turbiscan Lab® Expert optical analyzer, and they have been tested in vitro on NCTC 2544. The improved antioxidant activity of entrapped resveratrol was evaluated on keratinocyte cells as a function of its concentration. Finally, to really propose the resveratrol-loaded LCNs for topical use, the systems were gelled by using two different gelling agents, poloxamer P407 and carboxymethyl cellulose, to improve the contact time between skin and formulation. The rheological features of obtained gels were evaluated using two important methods (microrheology at rest and dynamic rheology), before testing their safety profile on human healthy volunteers. The obtained results showed the ability of LCNs to improve antioxidant activity of RSV and the gelled LCNs showed good rheological profiles. In conclusion, the results confirmed the potentiality of gelled resveratrol-loaded nanosystems for skin disease, mainly related to their antioxidant effects.

In recent years, bioactive compounds have been the focus of much interest in scientific research, due to their low toxicity and extraordinary properties. However, they possess poor solubility, low chemical stability, and unsustainable bioavailability. New drug delivery systems, and among them solid lipid nanoparticles (SLNs), could minimize these drawbacks. In this work, morin (MRN)-loaded SLNs (MRN-SLNs) were prepared using a solvent emulsification/diffusion method, using two different lipids, Compritol® 888 ATO (COM) or Phospholipon® 80H (PHO). SLNs were investigated for their physical–chemical, morphological, and technological (encapsulation parameters and in vitro release) properties. We obtained spherical and non-aggregated nanoparticles with hydrodynamic radii ranging from 60 to 70 nm and negative zeta potentials (about −30 mV and −22 mV for MRN-SLNs-COM and MRN-SLNs-PHO, respectively). The interaction of MRN with the lipids was demonstrated via μ-Raman spectroscopy, X-ray diffraction, and DSC analysis. High encapsulation efficiency was obtained for all formulations (about 99%, w/w), particularly for the SLNs prepared starting from a 10% (w/w) theoretical MRN amount. In vitro release studies showed that about 60% of MRN was released within 24 h and there was a subsequent sustained release within 10 days. Finally, ex vivo permeation studies with excised bovine nasal mucosa demonstrated the ability of SLNs to act as a penetration enhancer for MRN due to the intimate contact and interaction of the carrier with the mucosa.

Bicalutamide (BCL) is a nonsteroidal antiandrogen drug that represents an alternative to castration in the treatment of prostate cancer, due to its relatively long half-life and tolerable side effects. However, it possesses a very low water solubility that can affect its oral bioavailability. In this work, we developed inclusion complexes of BCL with the highly soluble hydroxypropyl-β-cyclodextrin (HP-β-CyD) and sulfobutylether-β-cyclodextrin (SBE-β-CyD) to increase the water solubility and anticancer activity of BCL. The inclusion complexes were prepared using the freeze-drying method and were then characterized in a solid state via differential scanning calorimetry and X-ray analysis and in solution via phase-solubility studies and UV-vis and NMR spectroscopy. The BCL/HP-β-CyD and BCL/SBE-β-CyD inclusion complexes were amorphous and rapidly dissolved in water. Both the 1H-NMR spectra and molecular modeling studies confirmed the penetration of the 2-(trifluoromethyl)benzonitrile ring of BCL within the cavity of both cyclodextrins (CyDs). Due to the consistent improvement of the water solubility of BCL, the inclusion complexes showed higher antiproliferative activity toward the human prostate androgen-independent cell lines, DU-145 and PC-3, with respect to free BCL. These results demonstrate the ability of HP-β-CyD and SBE-β-CyD to complex BCL, permitting the realization of liquid formulations with potentially high oral bioavailability and/or possible parenteral administration.

Idebenone (IDE) is a powerful antioxidant that is potentially active towards cerebral diseases, but its low water solubility and fast first pass metabolism reduce its accumulation in the brain, making it ineffective. In this work, we developed cyclodextrin-based chitosan nanospheres (CS NPs) as potential carriers for nose-to-brain targeting of IDE. Sulfobutylether-β-cyclodextrin (SBE-β-CD) was used as a polyanion for chitosan (CS) and as a complexing agent for IDE, permitting its encapsulation into nanospheres (NPs) produced in an aqueous solution. Overloading NPs were obtained by adding the soluble IDE/hydroxypropyl-β-CD (IDE/HP-β-CD) inclusion complex into the CS or SBE-β-CD solutions. We obtained homogeneous CS NPs with a hydrodynamic radius of about 140 nm, positive zeta potential (about +28 mV), and good encapsulation efficiency and drug loading, particularly for overloaded NPs. A biphasic release of IDE, finished within 48 h, was observed from overloaded NPs, whilst non-overloaded CS NPs produced a prolonged release, without a burst effect. In vitro biological studies showed the ability of CS NPs to preserve the antioxidant activity of IDE on U373 culture cells. Furthermore, Fourier transform infrared spectroscopy (FT-IR) demonstrated the ability of CS NPs to interact with the excised bovine nasal mucosa, improving the permeation of the drug and potentially favoring its accumulation in the brain.

Hydrogels have been extensively investigated to identify innovative formulations that can fulfill all the necessary purposes to improve local vaginal therapy through the mucosa. Herein, we propose in situ-forming lyotropic liquid crystals (LLCs) derived from a cheap and GRAS (generally recognized as safe) ingredient as an intravaginal delivery system. The system consists of a precursor solution loaded with sertaconazole nitrate as a model drug, which is able to easily swell in a stable three-dimensional structure by absorbing simulated vaginal fluid. Under polarized light microscopy the precursor solution and the formed phase of LLCs showed the typical textures belonging to anisotropic and an isotropic mesophases, respectively. A deep rheological investigation by Kinexus® Pro proved the stability and strength of the cubic phase, as well as its potential in mucoadhesion. In vitro degradation studies showed a slow matrix erosion, consistent with data obtained from lipophilic drug release studies in simulated vaginal fluid. Therefore, the suggested cubic phase based on lyotropic liquid crystals could represent a valid proposal as a vaginal drug delivery system due to its characteristics of resistance, adhesion and the possibility of providing a slow and controlled release of drugs directly at the administration site.

For many years, corneal transplantation has been the first-choice treatment for irreversible damage affecting the anterior part of the eye. However, the low number of cornea donors and cases of graft rejection highlighted the need to replace donor corneas with new biomaterials. Tissue engineering plays a fundamental role in achieving this goal through challenging research into a construct that must reflect all the properties of the cornea that are essential to ensure correct vision. In this review, the anatomy and physiology of the cornea are described to point out the main roles of the corneal layers to be compensated and all the requirements expected from the material to be manufactured. Then, a deep investigation of alginate as a suitable alternative to donor tissue was conducted. Thanks to its adaptability, transparency and low immunogenicity, alginate has emerged as a promising candidate for the realization of bioengineered materials for corneal regeneration. Chemical modifications and the blending of alginate with other functional compounds allow the control of its mechanical, degradation and cell-proliferation features, enabling it to go beyond its limits, improving its functionality in the field of corneal tissue engineering and regenerative medicine.

The natural healing capacity of the tendon tissue is limited due to the hypovascular and cellular nature of this tissue. So far, several conventional approaches have been tested for tendon repair to accelerate the healing process, but all these approaches have their own advantages and limitations. Regenerative medicine and tissue engineering are interdisciplinary fields that aspire to develop novel medical devices, innovative bioscaffold, and nanomedicine, by combining different cell sources, biodegradable materials, immune modulators, and nanoparticles for tendon tissue repair. Different studies supported the idea that bioscaffolds can provide an alternative for tendon augmentation with an enormous therapeutic potentiality. However, available data are lacking to allow definitive conclusion on the use of bioscaffolds for tendon regeneration and repairing. In this review, we provide an overview of the current basic understanding and material science in the field of bioscaffolds, nanomedicine, and tissue engineering for tendon repair.

The incidence of cancer is increasing dramatically, affecting all ages of the population and reaching an ever higher worldwide mortality rate. The lack of therapies’ efficacy is due to several factors such as a delay in diagnosis, tumor regrowth after surgical resection and the occurrence of multidrug resistance (MDR). Tumor-associated immune cells and the tumor microenvironment (TME) deeply affect the tumor’s progression, leading to several physicochemical changes compared to physiological conditions. In this scenario, macrophages play a crucial role, participating both in tumor suppression or progression based on the polarization of onco-suppressive M1 or pro-oncogenic M2 phenotypes. Moreover, much evidence supports the pivotal role of macrophage-derived extracellular vesicles (EVs) as mediators in TME, because of their ability to shuttle the cell–cell and organ–cell communications, by delivering nucleic acids and proteins. EVs are lipid-based nanosystems with a broad size range distribution, which reflect a similar composition of native parent cells, thus providing a natural selectivity towards target sites. In this review, we discuss the impact of macrophage-derived EVs in the cancer’s fate as well as their potential implications for the development of personalized anticancer nanomedicine.

Bergamot essential oil (BEO) and Ammonium glycyrrhizinate (AG), naturally derived compounds, have remarkable anti-inflammatory properties, thus making them suitable candidates for the treatment of skin disorders. Despite this, their inadequate physicochemical properties strongly compromise their topical application. Ultradeformable nanocarriers containing both BEO and AG were used to allow their passage through the skin, thus maximizing their therapeutic activity. Physicochemical characterization studies were performed using Zetasizer Nano ZS and Turbiscan Lab®. The dialysis method was used to investigate the release profile of the active compounds. In vivo studies were performed on human healthy volunteers through the X-Rite spectrophotometer. The nanosystems showed suitable features for topical cutaneous administration in terms of mean size, surface charge, size distribution, and long-term stability/storability. The co-delivery of BEO and AG in the deformable systems improved both the release profile kinetic of ammonium glycyrrhizinate and deformability properties of the resulting nanosystems. The topical cutaneous administration on human volunteers confirmed the efficacy of the nanosystems. In detail, BEO and AG-co-loaded ultradeformable vesicles showed a superior activity compared to that recorded from the ones containing AG as a single agent. These results are promising and strongly encourage a potential topical application of AG/BEO co-loaded nanocarriers for anti-inflammatory therapies.

The regeneration of cardiac tissue is a multidisciplinary research field aiming to improve the health condition of the post-heart attack patient. Indeed, myocardial tissue has a poor ability to self-regenerate after severe damage. The scientific efforts focused on the research of a biomaterial able to adapt to heart tissue, thus guaranteeing the in situ release of active substances or growth promoters. Many types of hydrogels were proposed for this purpose, showing several limitations. The aim of this study was to suggest a new usage for glyceryl monooleate-based lyotropic liquid crystals (LLCs) as a biocompatible and inert material for a myocardial application. The main advantages of LLCs are mainly related to their easy in situ injection as lamellar phase and their instant in situ transition in the cubic phase. In vivo studies proved the biocompatibility and the inertia of LLCs after their application on the myocardial tissue of mice. In detail, the cardiac activity was monitored through 28 days, and no significant alterations were recorded in the heart anatomy and functionality. Moreover, gross anatomy showed the ability of LLCs to be bio-degraded in a suitable time frame. Overall, these results permitted us to suppose a potential use of LLCs as materials for cardiac drug delivery.

Rutin is a natural compound with several pharmacological effects. Among these, antioxidant activity is one of the best known. Despite its numerous benefits, its topical application is severely limited by its physicochemical properties. For this reason, the use of suitable systems could be necessary to improve its delivery through skin, thus enhancing its pharmacological effects. In this regard, the aim of this work is to optimize the ethosomal dispersion modifying both lipid and ethanol concentrations and encapsulating different amounts of rutin. Characterization studies performed on the realized systems highlighted their great stability properties. Studies of encapsulation efficiency and loading degree allowed us to identify a better formulation (EE% 67.5 ± 5.2%, DL% 27 ± 1.7%), which was used for further analyses. The data recorded from in vitro studies showed that the encapsulation into these nanosystems allowed us to overcome the photosensitivity limitation of rutin. Indeed, a markable photostability of the loaded formulation was recorded, compared with that reported from the free rutin solution. The efficacy of the nanosystems was finally evaluated both in vitro on keratinocyte cells and in vivo on human healthy volunteers. The results confirmed the potentiality of rutin-loaded nanosystems for skin disease, mainly related to their anti-inflammatory and antioxidant effects.

Levofloxacin (LVF) is an antibacterial drug approved for the treatment of ocular infections. However, due to the low ocular bioavailability, high doses are needed, causing bacterial resistance. Polymeric nanospheres (NPs) loading antibiotic drugs represent the most promising approach to eradicate ocular infections and to treat pathogen resistance. In this study, we have developed chitosan NPs based on sulfobutyl-ether-β-cyclodextrin (CH/SBE-β-CD NPs) for ocular delivery of LVF. CH/SBE-β-CD NPs loading LVF were characterized in terms of encapsulation parameters, morphology, and sizes, in comparison to NPs produced without the macrocycle. Nuclear magnetic resonance and UV–vis spectroscopy studies demonstrated that SBE-β-CD is able to complex LVF and to influence encapsulation parameters of NPs, producing high encapsulation efficiency and LVF loading. The NPs were homogenous in size, with a hydrodynamic radius between 80 and 170 nm and positive zeta potential (ζ) values. This surface property could promote the interaction of NPs with the negatively charged ocular tissue, increasing their residence time and, consequently, LVF efficacy. In vitro, antibacterial activity against Gram-positive and Gram-negative bacteria showed a double higher activity of CH/SBE-β-CD NPs loading LVF compared to the free drug, suggesting that chitosan NPs based on SBE-β-CD could be a useful system for the treatment of ocular infections.

Ethosomes® are one of the main deformable vesicles proposed to overcome the stratum corneum. They are composed of lecithin, ethanol and water, resulting in round vesicles characterized by a narrow size distribution and a negative surface charge. Taking into account their efficiency to deliver drugs into deeper skin layers, the current study was designed to evaluate the influence of different lipids on the physico-chemical features of traditional ethosomes in the attempt to influence their fate. Three lipids (DOPE, DSPE and DOTAP) were used for the study, but only DOTAP conferred a net positive charge to ethosomes, maintaining a narrow mean size lower than 300 nm and a good polydispersity index. Stability and in vitro cytotoxic studies have been performed using Turbiscan Lab analysis and MTT dye exclusion assay, respectively. Data recorded demonstrated the good stability of modified ethosomes and a reasonable absence of cell mortality when applied to human keratinocytes, NCTC 2544, which are used as a cell model. Finally, the best formulations were selected to evaluate their ability to encapsulate drugs, through the use of model compounds. Cationic ethosomes encapsulated oil red o and rhodamine b in amounts comparable to those recorded from conventional ethosomes (over 50%). Results recorded from this study are encouraging as cationic ethosomes may open new opportunities for skin delivery.

pH-sensitive nonionic surfactant vesicles (niosomes) by polysorbate-20 (Tween-20) or polysorbate-20 derivatized by glycine (added as pH sensitive agent), were developed to deliver Ibuprofen (IBU) and Lidocaine (LID). For the physical-chemical characterization of vesicles (mean size, size distribution, zeta potential, vesicle morphology, bilayer properties and stability) dynamic light scattering (DLS), small angle X-ray scattering and fluorescence studies were performed. Potential cytotoxicity was evaluated on immortalized human keratinocyte cells (HaCaT) and on immortalized mouse fibroblasts Balb/3T3. In vivo antinociceptive activity (formalin test) and anti-inflammatory activity tests (paw edema induced by zymosan) in murine models were performed on drug-loaded niosomes. pH-sensitive niosomes were stable in the presence of 0 and 10% fetal bovine serum, non-cytotoxic and able to modify IBU or LID pharmacological activity in vivo. The synthesis of stimuli responsive surfactant, as an alternative to add pH-sensitive molecules to niosomes, could represent a promising delivery strategy for anesthetic and anti-inflammatory drugs.

Paclitaxel (PTX) is one of the most successful antineoplastic drugs and is widely used for the treatment of many forms of advanced and refractory cancer. Unfortunately, various drawbacks including non-selective cytotoxicity, poor water solubility and low bioavailability limit its clinical use. The aim of this study was to characterize a novel colloidal system made up of the natural protein zein, that would be able to efficiently retain the anticancer compound and increase its in vitro pharmacological effects. In fact, zein has promising characteristics that render it a potential material to be used in drug delivery application. The influences of temperature, pH and serum incubation on the stability of these particles, entrapment efficiency of PTX and in vitro toxicity on different cancer cell lines were evaluated. The nanosystems containing PTX demonstrated suitable storage stability, and were not destabilized by temperatures of up to 50 °C, pH alterations, the freeze-drying process or serum proteins. The encapsulation of PTX did not destabilize the structure of the zein nanoparticles and a suitable drug entrapment efficiency resulted. PTX-loaded zein nanoparticles showed an increased toxicity on different cancer cell lines with respect to the free drug, confirming its potential application in preclinical and clinical investigations.

c-Kit, a type III receptor tyrosine kinase (RTK), is involved in multiple intracellular signaling whereby it is mainly considered a stem cell factor receptor, which participates in vital functions of the mammalian body, including the human. Furthermore, c-kit is a necessary yet not sufficient marker to detect and isolate several types of tissue-specific adult stem cells. Accordingly, c-kit was initially used as a marker to identify and enrich for adult cardiac stem/progenitor cells (CSCs) that were proven to be clonogenic, self-renewing and multipotent, being able to differentiate into cardiomyocytes, endothelial cells and smooth muscle cells in vitro as well as in vivo after myocardial injury. Afterwards it was demonstrated that c-kit expression labels a heterogenous cardiac cell population, which is mainly composed by endothelial cells while only a very small fraction represents CSCs. Furthermore, c-kit as a signaling molecule is expressed at different levels in this heterogenous c-kit labeled cardiac cell pool, whereby c-kit low expressers are enriched for CSCs while c-kit high expressers are endothelial and mast cells. This heterogeneity in cell composition and expression levels has been neglected in recent genetic fate map studies focusing on c-kit, which have claimed that c-kit identifies cells with robust endothelial differentiation potential but with minimal if not negligible myogenic commitment potential. However, modification of c-kit gene for Cre Recombinase expression in these Cre/Lox genetic fate map mouse models produced a detrimental c-kit haploinsufficiency that prevents efficient labeling of true CSCs on one hand while affecting the regenerative potential of these cells on the other. Interestingly, c-kit haploinsufficiency in c-kit-deficient mice causes a worsening myocardial repair after injury and accelerates cardiac aging. Therefore, these studies have further demonstrated that adult c-kit-labeled CSCs are robustly myogenic and that the adult myocardium relies on c-kit expression to regenerate after injury and to counteract aging effects on cardiac structure and function.

Ethosomes® have been proposed as potential intra-articular drug delivery devices, in order to obtain a longer residence time of the delivered drug in the knee joint. To this aim, the conventional composition and preparation method were modified. Ethosomes® were prepared by using a low ethanol concentration and carrying out a vesicle extrusion during the preparation. The modified composition did not affect the deformability of ethosomes®, a typical feature of this colloidal vesicular topical carrier. The maintenance of sufficient deformability bodes well for an effective ethosome® application in the treatment of joint pathologies because they should be able to go beyond the pores of the dense collagen II network. The investigated ethosomes® were inserted in a three-dimensional network of thermo-sensitive poloxamer gel (EtoGel) to improve the residence time in the joint. Rheological experiments evidenced that EtoGel could allow an easy intra-articular injection at room temperature and hence transform itself in gel form at body temperature into the joint. Furthermore, EtoGel seemed to be able to support the knee joint during walking and running. In vitro studies demonstrated that the amount of used ethanol did not affect the viability of human chondrocytes and nanocarriers were also able to suitably interact with cells.

Linoleic and oleic acids are natural unsaturated fatty acids involved in several biological processes and recently studied as structural components of innovative nanovesicles. The use of natural components in the pharmaceutical field is receiving growing attention from the scientific world. The aim of this research work is to design, to perform physico-chemical characterization and in vitro/in vivo studies of unsaturated fatty acids vesicles containing ammonium glycyrrhizinate, obtaining a new topical drug delivery system. The chosen active substance is well known as an anti-inflammatory compound, but its antioxidant activity is also noteworthy. In this way, the obtained nanocarriers are totally natural vesicles and they have shown to have suitable physico-chemical features for topical administration. Moreover, the proposed nanocarriers have proven their ability to improve the in vitro percutaneous permeation and antioxidant activity of ammonium glycyrrhizinate on human keratinocytes (NCTC 2544 cells). In vivo studies, carried out on human volunteers, have demonstrated the biocompatibility of unsaturated fatty acid vesicles toward skin tissue, indicating a possible clinical application of unsaturated fatty acid vesicles for the treatment of topical diseases.

Periodontal diseases are multifactorial disorders, mainly due to severe infections and inflammation which affect the tissues (i.e., gum and dental bone) that support and surround the teeth. These pathologies are characterized by bleeding gums, pain, bad breath and, in more severe forms, can lead to the detachment of gum from teeth, causing their loss. To date it is estimated that severe periodontal diseases affect around 10% of the population worldwide thus making necessary the development of effective treatments able to both reduce the infections and inflammation in injured sites and improve the regeneration of damaged tissues. In this scenario, the use of 3D scaffolds can play a pivotal role by providing an effective platform for drugs, nanosystems, growth factors, stem cells, etc., improving the effectiveness of therapies and reducing their systemic side effects. The aim of this review is to describe the recent progress in periodontal regeneration, highlighting the influence of materials’ properties used to realize three-dimensional (3D)-scaffolds, their bio-physical characteristics and their ability to provide a biocompatible platform able to embed nanosystems.

In the last few decades, the combination between nanotechnology and nutraceutics has gained the attention of several research groups. Nutraceuticals are considered as active compounds, abundant in natural products, showing beneficial effects on human health. Unfortunately, the uses, and consequently the health benefits, of many nutraceutical products are limited by their unsuitable chemico-physical features. For example, many nutraceuticals are characterized by low water solubility, low stability and high susceptibility to light and oxygen, poor absorption and potential chemical modifications after their administration. Based on the potential efficacy of nutraceuticals and on their limiting features, nanotechnology could be considered a revolutionary innovation in empowering the beneficial properties of nutraceuticals on human health, thus enhancing their efficacy in several diseases. For this reason, nanotechnology could represent a new frontier in supplementary food. In this review, the most recent nanotechnological approaches are discussed, focusing on their ability to improve the bioavailability of the most common nutraceuticals, providing an overview regarding both the advantages and the possible limitations of the use of several nanodelivery systems. In fact, although the efficacy of smart nanocarriers in improving health benefits deriving from nutraceuticals has been widely demonstrated, the conflicting opinions on the mechanism of action of some nanosystems still reduce their applicability in the therapeutic field.

Ferulic acid is a derivative of cinnamic acid showing efficacious anti-oxidant activity. It catalyzes the stable phenoxy radical formation, upon absorption of ultraviolet light, giving the strength to ferulic acid for terminating free radical chain reactions. Ultraviolet rays are one of the most dangerous factors that daily assault the skin, causing excessive generation of reactive oxygen species (ROS), which are regarded to be important contributors to a variety of cutaneous alterations. The skin possesses endogenous antioxidant defense systems, but the excess of ROS leads to an oxidant–antioxidant imbalance. Although ferulic acid is daily introduced in human organism with the diet, its bioavailability after oral administration is poor, particularly in the skin. The aim of this investigation was to evaluate three types of emulsions (W/O/W multiple emulsions and two simple emulsions) as suitable formulations for topical application of the active compound. In vitro studies were performed to investigate the stability and release profiles of these systems. Multiple emulsions showed great stability and the best ability to carry and release ferulic acid. In vivo evaluations highlighted their best capability to treat UV-B-induced erythema. These findings suggested multiple emulsions as an innovative and more efficient vehicle for topical application of ferulic acid.

This study was aimed at preparing and characterizing solid lipid nanoparticles loading rutin (RT-SLNs) for the treatment of oxidative stress-induced diseases. Phospholipon 80H® as a solid lipid and Polysorbate 80 as surfactant were used for the SLNs preparation, using the solvent emulsification/diffusion method. We obtained spherical RT-SLNs with low sizes, ranging from 40 to 60 nm (hydrodynamic radius) for the SLNs prepared starting from 2% and 5% (w/w) theoretical amount. All prepared formulations showed negative zeta-potential values. RT was efficiently encapsulated within SLNs, obtaining high encapsulation efficiency and drug content percentages, particularly for SLNs prepared with a 5% theoretical amount of RT. In vitro release profiles and analysis of the obtained data applying different kinetic models revealed Fickian diffusion as the main mechanism of RT release from the SLNs. The morphology of RT-SLNs was characterized by scanning electron microscopy (SEM), whereas the interactions between RT and the lipid matrix were investigated by Raman spectroscopy, evidencing spectral modifications of characteristic bands of RT due to the establishment of new interactions. Finally, antioxidant activity assay on human glioblastoma astrocytoma (U373) culture cells showed a dose-dependent activity for RT-SLNs, particularly at the highest assayed dose (50 μM), whereas the free drug showed the lesser activity.

Ufasomes are unsaturated fatty acid liposomes made up of oleic and linoleic acids, natural components required in various biological processes. This kind of nanocarrier is characterized by a simple and dynamic structure and is able to improve the bioavailability of unsaturated fatty acids. The aim of this investigation was to evaluate ufasomes as natural compound delivery systems to deliver oleuropein and improve its antioxidant activity. Oleuropein is a phenolic compound mainly present in olives and olive oil, with several biological properties, such as the antioxidant activity. However, to improve their biological activity, antioxidant compounds should be able to cross cell membranes and uniformly incorporate in cells. Because of the great similarity between their constituents and cell membranes, ufasomes could be advantageous carriers for oleuropein delivery. The physico-chemical characteristics of ufasomes were investigated. A regular shape was shown by transmission electron microscopy studies, while the mean sizes were dependent on the ufasomes composition. In vitro studies highlighted that empty ufasomes did not lead to cell mortality at the tested concentrations and a good carrier internalization in CaCo-2 cells, further studies in vitro studies demonstrated that oleuropein-loaded ufasomes were able to enhance the antioxidant activity of the free active substance making this carrier a suitable one for nutraceutical application.

The topical administration of active compounds represents an advantageous strategy to reach the various skin components as well as its appendages. Pilosebaceous follicles are skin appendages originating in the deeper skin layers. They are very difficult to target, and hence higher active dosages are generally required to achieve effective biological responses, thus favoring the rise of side effects. The aim of this work was to design a supramolecular colloidal carrier, i.e., a liquid crystal nanocarrier, for the selective delivery of active compounds into the pilosebaceous follicle. This nanocarrier showed mean sizes of ~80 nm, a good stability, a negative surface charge, and great safety properties. In vitro studies highlighted its ability to contain and release different substances and to successfully permeate the skin. Minoxidil was encapsulated in the nanocarriers and the in vivo biological effect was compared with a conventional dosage form. Minoxidil-loaded liquid crystal nanocarrier was able to selectively reach the pilosebaceous follicle, thus allowing an increased biological effectiveness of the delivered active in terms of biological response, duration of the biological effects, and reduction of collaterals. Our investigation showed that liquid crystal nanocarriers represent a promising device for the treatment of different pilosebaceous follicular impairments/diseases.

Cardiovascular disease (CVD) remains the leading cause of death in Western countries. Post-myocardial infarction heart failure can be considered a degenerative disease where myocyte loss outweighs any regenerative potential. In this scenario, regenerative biology and tissue engineering can provide effective solutions to repair the infarcted failing heart. The main strategies involve the use of stem and progenitor cells to regenerate/repair lost and dysfunctional tissue, administrated as a suspension or encapsulated in specific delivery systems. Several studies demonstrated that effectiveness of direct injection of cardiac stem cells (CSCs) is limited in humans by the hostile cardiac microenvironment and poor cell engraftment; therefore, the use of injectable hydrogel or pre-formed patches have been strongly advocated to obtain a better integration between delivered stem cells and host myocardial tissue. Several approaches were used to refine these types of constructs, trying to obtain an optimized functional scaffold. Despite the promising features of these stem cells’ delivery systems, few have reached the clinical practice. In this review, we summarize the advantages, and the novelty but also the current limitations of engineered patches and injectable hydrogels for tissue regenerative purposes, offering a perspective of how we believe tissue engineering should evolve to obtain the optimal delivery system applicable to the everyday clinical scenario.

There is a constant increase in the attention being paid to food quality and the effects of food on human health among consumers. Vegetable milk is among the foods whose consumption worldwide has increased because, when compared to animal-derived milk, it offers numerous benefits for human health. The aim of this research work was to use vegetable milk to obtain yogurt-like products enriched with different concentrations of carob seed flour, which has a double function: to modify, and thus perfect, the rheological characteristics of vegetable-milk-based yogurt-like samples and to increase their nutritional value. The rheological parameters of the obtained samples were studied both in static and dynamic conditions, confirming that carob seed flour, especially at the highest used concentrations (0.75%; 1%), allows one to obtain products characterized by a good stability and suitable rheological characteristics. The obtained yogurt-like products may also be consumed by celiac subjects, since carob seed flour is a gluten-free flour, and allow celiac consumers to combine a gluten-free diet with a diet free of animal derivatives. Furthermore, the addition of carob flour allows one to obtain a tasty product thanks to the sweet taste of the carob seed flour.

The controlled release of a compound entrapped in a biocompatible formulation is a sought-after goal in modern pharmaceutical technology. Zein is a hydrophobic protein which has several advantageous properties that make it suitable for use as a biocompatible and degradable material under physiological conditions. It is, therefore, proposed for different biomedical and pharmaceutical applications. In particular, due to its gelling properties, it can be used to form a polymeric network able to preserve biomolecules from harsh environments. The current study was designed to investigate the influence of different probes on the rheological properties of gels made up of zein, in order to characterize the systems as a function of the polymer concentration. Four model compounds characterized by different physico-chemical properties were entrapped in zein gels, and different behaviors (viscoelastic or pronounced solid-like characteristics) of the systems were observed. Zein-based gels showed various release profiles of the encapsulated compounds, suggesting that there are different interaction rates between the probes and the polymeric matrix.

Rutin is a flavone glycoside contained in many plants, and exhibits antioxidant, anti-inflammatory, anticancer, and wound-healing properties. The main disadvantage related to the use of this molecule for pharmaceutical application is its poor bioavailability, due to its low solubility in aqueous media. Poloxamer 407-hydrogels show interesting thermo-sensitive properties that make them attractive candidates as pharmaceutical formulations. The hydrophobic domains in the chemical structure of the copolymer, a polymer made up of two or more monomer species, are useful for retaining poorly water-soluble compounds. In this investigation various poloxamer 407-based hydrogels containing rutin were developed and characterized as a function of the drug concentration. In detail, the Turbiscan stability index, the micro- and dynamic rheological profiles and in vitro drug release were investigated and discussed. Rutin (either as a free powder or solubilized in ethanol) did not modify the stability or the rheological properties of these poloxamer 407-based hydrogels. The drug leakage was constant and prolonged for up to 72 h. The formulations described are expected to represent suitable systems for the in situ application of the bioactive as a consequence of their peculiar versatility.

Poloxamer 407 copolymer is a versatile and widely used thermo-reversible material. Its use has many advantages, such as bio-adhesion, enhanced solubilization of poorly water-soluble drugs and many applications fields like oral, rectal, topical, nasal drug administration. Hydrogels made up of Poloxamer 407 are characterized by specific rheological features, which are affected by temperature, concentration and presence of other compounds. A strategic approach in topical therapeutic treatments may be the inclusion of drug delivery systems, such as ethosomes, transfersomes and niosomes, into hydrogel poloxamer formulation. The evaluation of the interaction between colloidal carriers and the Poloxamer 407 hydrogel network is essential for a suitable design of an innovative topical dosage form. For this reason, the Rheolaser Master™, based on diffusing wave spectroscopy, and a Kinexus Rotational Rheometer were used to evaluate the influence of nanocarriers on the microrheological features of hydrogels. The advantages of the Rheolaser Master™ analyzer are: (i) its ability to determine viscoelastic parameter, without altering or destroying the sample and at rest (zero shear); (ii) possibility of aging analysis on the same sample. This study provide evidence that vesicular systems do not influence the rheological features of the gel, supporting the possibility to encapsulate an innovative system into a three-dimensional network.

Idebenone (IDE) is an antioxidant drug active at the level of the central nervous system (CNS), whose poor water solubility limits its clinical application. An IDE/2-hydroxypropyl-β-cyclodextrin (IDE/HP-β-CD) inclusion complex was investigated by combining experimental methods and theoretical approaches. Furthermore, biological in vitro/ex vivo assays were performed. Phase solubility studies showed an AL type diagram, suggesting the presence of a 1:1 complex with high solubility. Scanning electron microscopy (SEM) allowed us to detect the morphological changes upon complexation. The intermolecular interactions stabilizing the inclusion complex were experimentally characterized by exploring the complementarity of Fourier-transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) with mid-infrared light, Fourier-transform near-infrared (FT-NIR) spectroscopy, and Raman spectroscopy. From the temperature evolution of the O−H stretching band of the complex, the average enthalpy ΔHHB of the hydrogen bond scheme upon inclusion was obtained. Two-dimensional (2D) rotating frame Overhauser effect spectroscopy (ROESY) analysis and computational studies involving molecular modeling and molecular dynamics (MD) simulation demonstrated the inclusion of the quinone ring of IDE inside the CD ring. In vitro/ex vivo studies evidenced that complexation produces a protective effect of IDE against the H2O2-induced damage on human glioblastoma astrocytoma (U373) cells and increases IDE permeation through the excised bovine nasal mucosa.

Biogenic amines (BAs), polyphenols, and aroma compounds were determined by chromatographic techniques in cocoa beans of different geographical origin, also considering the effect of roasting (95, 110, and 125 °C). In all samples, methylxantines (2.22−12.3 mg kg−1) were the most abundant followed by procyanidins (0.69−9.39 mg kg−1) and epicatechin (0.16−3.12 mg kg−1), all reduced by heat treatments. Volatile organic compounds and BAs showed variable levels and distributions. Although showing the highest BAs total content (28.8 mg kg−1), Criollo variety presented a good aroma profile, suggesting a possible processing without roasting. Heat treatments influenced the aroma compounds especially for Nicaragua sample, increasing more than two-fold desirable aldehydes and pyrazines formed during the Maillard cascade and the Strecker degradation. As the temperature increased, the concentration of BAs already present in raw samples increased as well, although never reaching hazardous levels.

In the last few years, essential oils (EOs) derived from plants have aroused great interest due to their well-known antimicrobial activity. Unfortunately, they present several limitations in their use, such as photosensitivity, temperature sensitivity, high volatility, and poor water solubility. The encapsulation technique represents a good solution to these problems and ensures protection of the functional properties of essential oils. In this work, bergamot essential oil (BEO) and sweet orange essential oil (OEO) loaded-Eudragit® RS 100 (EuRS100) nanoparticles (NPs) were prepared by using the nanoprecipitation technique. We obtained nanoparticles characterized by a mean diameter of 57 to 208 nm and a positive surface charge (39 to 74 mV). The antibacterial activity of the obtained systems against Escherichia coli was in vitro investigated. We demonstrated that both orange and bergamot essential oils were successfully encapsulated and our nanoparticles have good antibacterial activity. Finally, in order to evaluate the potential applicability of OEONps to prolong fresh orange juice shelf-life, survival of E. coli during a storage period of one week at 25 °C was investigated: Orange essential oil-loaded nanoparticles (OEONPs) have been able to prolong the orange juice shelf life.

Embedding of active substances in supramolecular systems has as the main goal to ensure the controlled release of the active ingredients. Whatever the final architecture or entrapment mechanism, modeling of release is challenging due to the moving boundary conditions and complex initial conditions. Despite huge diversity of formulations, diffusion phenomena are involved in practically all release processes. The approach in this paper starts, therefore, from mathematical methods for solving the diffusion equation in initial and boundary conditions, which are further connected with phenomenological conditions, simplified and idealized in order to lead to problems which can be analytically solved. Consequently, the release models are classified starting from the geometry of diffusion domain, initial conditions, and conditions on frontiers. Taking into account that practically all solutions of the models use the separation of variables method and integral transformation method, two specific applications of these methods are included. This paper suggests that “good modeling practice„ of release kinetics consists essentially of identifying the most appropriate mathematical conditions corresponding to implied physicochemical phenomena. However, in most of the cases, models can be written but analytical solutions for these models cannot be obtained. Consequently, empiric models remain the first choice, and they receive an important place in the review.

In this study, we investigated the release kinetic of fluorescein from colloidal liquid crystals made from monoglyceride and different non-ionic surfactants. The crystals were physicochemically characterized and the release experiments were carried out under the sink conditions, while mathematical models were described as extrapolations from solutions of the diffusion equation, in different initial and boundary conditions imposed by pharmaceutical formulations. The diffusion equation was solved using Laplace and Fourier transformed functions for release kinetics from infinite reservoirs in a semi-infinite medium. Solutions represents a general square root law and can be applied for the release kinetic of fluorescein from lyotropic colloidal liquid crystals. Akaike, Schwartz, and Imbimbo criteria were used to establish the appropriate mathematical model and the hierarchy of the performances of different models applied to the release experiments. The Fisher statistic test was applied to obtain the significance of differences among mathematical models. Differences of mathematical criteria demonstrated that small or no significant statistic differences were carried out between the various applied models and colloidal formulations. Phenomenological models were preferred over the empirical and semi-empirical ones. The general square root model shows that the diffusion-controlled release of fluorescein is the mathematical models extrapolated for lyotropic colloidal liquid crystals.

Hydrogels are three-dimensional networks of hydrophilic polymers able to absorb and retain a considerable amount of water or biological fluid while maintaining their structure. Among these, thermo-sensitive hydrogels, characterized by a temperature-dependent sol–gel transition, have been massively used as drug delivery systems for the controlled release of various bioactives. Poloxamer 407 (P407) is an ABA-type triblock copolymer with a center block of hydrophobic polypropylene oxide (PPO) between two hydrophilic polyethyleneoxide (PEO) lateral chains. Due to its unique thermo-reversible gelation properties, P407 has been widely investigated as a temperature-responsive material. The gelation phenomenon of P407 aqueous solutions is reversible and characterized by a sol–gel transition temperature. The nanoencapsulation of drugs within biocompatible delivery systems dispersed in P407 hydrogels is a strategy used to increase the local residence time of various bioactives at the injection site. In this mini-review, the state of the art of the most important mixed systems made up of colloidal carriers localized within a P407 hydrogel will be provided in order to illustrate the possibility of obtaining a controlled release of the entrapped drugs and an increase in their therapeutic efficacy as a function of the biomaterial used.

Poloxamer 407, also known by the trademark Pluronic® F127, is a water-soluble, non-ionic triblock copolymer that is made up of a hydrophobic residue of polyoxypropylene (POP) between the two hydrophilic units of polyoxyethylene (POE). Poloxamer 407-based hydrogels exhibit an interesting reversible thermal characteristic. That is, they are liquid at room temperature, but they assume a gel form when administered at body temperature, which makes them attractive candidates as pharmaceutical drug carriers. These systems have been widely investigated in the development of mucoadhesive formulations because they do not irritate the mucosal membranes. Based on these mucoadhesive properties, a simple administration into a specific compartment should maintain the required drug concentration in situ for a prolonged period of time, decreasing the necessary dosages and side effects. Their main limitations are their modest mechanical strength and, notwithstanding their bioadhesive properties, their tendency to succumb to rapid elimination in physiological media. Various technological approaches have been investigated in the attempt to modulate these properties. This review focuses on the application of poloxamer 407-based hydrogels for mucosal drug delivery with particular attention being paid to the latest published works.

Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP). Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase. Nanoliposomes, made up of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine monohydrate (DPPC), cholesterol, and N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-mPEG2000) (6:3:1 molar ratio), were characterized by a mean diameter of ~100 nm, a very low polydispersity index (~0.1) and a negative surface charge. The drugs did not influence the physico-chemical properties of the systems and were efficiently retained in the colloidal structure. By using cell count and MTT assay, we found a significant reduction of the viability in both cell lines following 24 h treatment with both nanoliposomal-encapsulated drugs, notably greater than the effect of the free drugs. Our findings demonstrate that nanoliposomes increase the antiproliferative activity of phosphodiesterase-5 inhibitors, providing a useful novel formulation for the treatment of thyroid carcinoma.