Skin Tolerability of Oleic Acid Based Nanovesicles Designed for the Improvement of Icariin and Naproxen Percutaneous Permeation.

Deformable nanovesicles have a crucial role in topical drug delivery through the skin, due to their capability to pass intact the stratum corneum and epidermis (SCE) and significantly increase the efficacy and accumulation of payloads in the deeper layers of the skin. Namely, lipid-based ultradeformable nanovesicles are versatile and load bioactive molecules with different physicochemical properties. For this reason, this study aims to make oleic acid based nanovesicles (oleosomes) for the codelivery of icariin and sodium naproxen and increase their permeation through the skin. Oleosomes have suitable physicochemical properties and long-term stability for a potential dermal or transdermal application. The inclusion of oleic acid in the lipid bilayer increases 3-fold the deformable properties of oleosomes compared to conventional liposomes and significantly improves the percutaneous permeation of icariin and sodium naproxen through the human SCE membranes compared to hydroalcoholic solutions of both drugs. The tolerability studies on human volunteers demonstrate that oleosomes are safer and speed up the recovery of transepidermal water loss (TEWL) baselines compared to saline solution. These results highlight promising properties of icariin/sodium naproxen coloaded oleosomes for the treatment of skin disorders and suggest the potential future applications of these nanovesicles for further in vivo experiments.

Gelled Liquid Crystal Nanocarriers for Improved Antioxidant Activity of Resveratrol.

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.

Perspective use of bio-adhesive liquid crystals as ophthalmic drug delivery systems.

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.

Solid Lipid Nanoparticles Containing Morin: Preparation, Characterization, and Ex Vivo Permeation Studies.

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.

Injectable Drug Delivery Systems for Osteoarthritis and Rheumatoid Arthritis.

Joint diseases are one of the most common causes of morbidity and disability worldwide. The main diseases that affect joint cartilage are osteoarthritis and rheumatoid arthritis, which require chronic treatment focused on symptomatic relief. Conventional drugs administered through systemic or intra-articular routes have low accumulation and/or retention in articular cartilage, causing dose-limiting toxicities and reduced efficacy. Therefore, there is an urgent need to develop improved strategies for drug delivery, in particular, the use of micro- and nanotechnology-based methods. Encapsulation of therapeutic agents in delivery systems reduces drug efflux from the joint and protects against rapid cellular and enzymatic clearance following intra-articular injection. Consequently, the use of drug delivery systems decreases side effects and increases therapeutic efficacy due to enhanced drug retention in the intra-articular space. Additionally, the frequency of intra-articular administration is reduced, as delivery systems enable sustained drug release. This review summarizes various advanced drug delivery systems, such as nano- and microcarriers, developed for articular cartilage diseases.

Bicalutamide Anticancer Activity Enhancement by Formulation of Soluble Inclusion Complexes with Cyclodextrins.

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-ß-cyclodextrin (HP-ß-CyD) and sulfobutylether-ß-cyclodextrin (SBE-ß-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-ß-CyD and BCL/SBE-ß-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-ß-CyD and SBE-ß-CyD to complex BCL, permitting the realization of liquid formulations with potentially high oral bioavailability and/or possible parenteral administration.

Oleic acid-based vesicular nanocarriers for topical delivery of the natural drug thymoquinone: Improvement of anti-inflammatory activity.

The topical administration of a drug compound remains the first choice for the treatment of many local skin ailments. Many skin diseases can be treated by applying the active formulation directly to the skin, but unfortunately some drugs are unable to overcome the stratum corneum and exert their pharmacological action. An example is thymoquinone, a naturally derived drug obtained from Nigella sativa L. and potentially effective in the treatment of inflammatory and oxidative skin conditions. Since its physico-chemical properties are not suitable for overcoming the stratum corneum, we wanted to circumvent the problem by proposing new lipid-based nanovesicles called "oleoethosomes", made up of naturally derived ingredients, for its delivery. Among several formulations of oleoethosomes, the sample made up of 2% (w/w) oleic acid:PL90G 1:1 (molar ratio), and ethanol 15% showed the best physico-chemical characteristics and above all it showed the capacity to contain a suitable amount of thymoquinone (2 mg/ml). The formulation was tested in vitro on stratum corneum and viable epidermis membranes confirming its ability to induce the passage of thymoquinone through the human stratum corneum and to act as a permeation enhancer. In fact, it showed thymoquinone permeation values of 22.63 ± 1.49% regarding the applied drug amount. Oleoethosomes were compared with oleosomes, another kind of naturally derived nanosystems but free of ethanol. The experimental data confirmed that ethanol was an important component that enhanced the activity of the oleoethosomes when tested on the skin of healthy volunteers. The thymoquinone-loaded oleoethosome treatment demonstrated a significantly greater extent of anti-inflammatory activity than the treatment with thymoquinone-loaded oleosomes or the conventional dosage form of the drug. These in vivo results confirmed the synergic effect between oleic acid and ethanol on the lipid and protein compartments of the outermost skin layer, thus promoting a greater penetration capacity.

In Situ Swelling Formulation of Glycerol-Monooleate-Derived Lyotropic Liquid Crystals Proposed for Local Vaginal Application.

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.

Alginate-Based Composites for Corneal Regeneration: The Optimization of a Biomaterial to Overcome Its Limits.

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.

A comparison between silicone-free and silicone-based emulsions: Technological features and in vivo evaluation.

OBJECTIVE: Nowadays, the use of silicones in cosmetic formulation is still controversial, given that "natural" or "biodegradable" components are preferred. Often, the exclusion and/or the discrimination of these excipients from cosmetic field are unmotivated because all things cannot be painted with the same brush. Hence, we want to bring to light and underline the advantages of including silicones in cosmetic emulsions, refuting and debunking some myths related to their use. METHODS: Silicone-free and silicone-based emulsions were obtained within an easy homogenization process. Droplet size distribution was assessed by laser diffraction particle size analyser Mastersizer 2000™, and by optical microscopy. The long-time stability profiles were investigated thanks to the optical analyser Turbiscan® Lab Expert. Diffusing wave spectroscopy (DWS) by Rheolaser Master™ and frequency sweep measurements by Kinexus® Pro Rotational Rheometer were carried out to assess a full rheological characterization. In vivo studies were carried out by the evaluation of Trans Epidermal Water Loss (TEWL) over time on healthy human volunteers. A skin feeling rating was collected from the same volunteers by questionnaire. RESULTS: From size distribution analysis, a better coherence of data appeared for silicone-based emulsion, as the size of the droplets was kept unchanged after 1 month, as well as the uniformity parameter. Morphological investigation confirmed a homogenous droplet distribution for both samples. Silicones enhanced the viscosity, compactness and strength of the cream, providing a suitable stability profile both at room temperature and when heated at 40°C. The solid-like viscoelastic behaviour was assessed in the presence of dynamic oscillatory stresses. The monitoring of TEWL over time demonstrated non-occlusive properties of emulsions containing silicones, the values of which were comparable to the negative control. Silicone-based emulsions gained higher scores from the volunteers in silkiness, freshness and softness features, while lower scores were obtained in greasiness compared to silicone-free emulsions. No cases of irritation were recorded by the candidates. CONCLUSION: The presence of specific silicones inside a cosmetic product improved its technological characteristics. The rheological identity and the stability feature showed the real suitability of prepared emulsion as a cosmetic product. Moreover, this study demonstrated that silicone-based emulsions are safe for the skin and did not cause skin occlusion. Improved skin sensations are registered by potential consumers when silicones are included in the formulation.

OBJECTIF: De nos jours, l'utilisation de silicones dans la formulation cosmétique reste controversée, étant donné que les ingrédients «naturels¼ ou «biodégradables¼ sont privilégiés. Souvent, l'exclusion et/ou la discrimination de ces excipients du domaine cosmétique ne sont pas motivées, parce que tous les éléments ne peuvent pas être logés à la même enseigne. Par conséquent, nous souhaitons mettre en évidence et souligner les avantages de l'inclusion des silicones dans les émulsions cosmétiques, tout en réfutant et en démystifiant certains mythes liés à leur utilisation. MÉTHODES: Des émulsions sans silicone et des émulsions à base de silicone ont été obtenues dans le cadre d'un processus d'homogénéisation facile. La distribution des tailles de gouttelettes a été évaluée par diffraction laser avec le granulomètre Mastersizer 2000™ et par microscopie optique. Les profils de stabilité à long terme ont été étudiés grâce à l'analyseur optique Turbiscan® Lab Expert. La spectroscopie par diffusion d'ondes (Diffusing Wave Spectroscopy, DWS) par le Rheolaser Master™ et les mesures de balayage de fréquence par le rhéomètre rotatif Kinexus® Pro ont été réalisées pour évaluer une caractérisation rhéologique complète. Des études in vivo ont été menées par le biais de l'évaluation de la perte d'eau transépidermique (PETE) au fil du temps sur des volontaires humains en bonne santé. Une évaluation de la sensation cutanée a été recueillie auprès des mêmes volontaires par le biais d'un questionnaire. RÉSULTATS: L'analyse de la distribution des tailles a révélé une meilleure cohérence des données pour l'émulsion à base de silicone, car la taille des gouttelettes a été maintenue inchangée après 1 mois, ainsi que le paramètre d'uniformité. L'investigation morphologique a confirmé une distribution homogène des gouttelettes pour les deux échantillons. Les silicones ont amélioré la viscosité, la densité et la résistance de la crème, offrant ainsi un profil de stabilité approprié aussi bien à température ambiante qu'après chauffage à 40°C. Le comportement viscoélastique analogue à celui d'un solide a été évalué en présence de contraintes oscillatoires dynamiques. Le suivi de la perte d'eau transépidermique (PETE) au fil du temps a établi des propriétés non occlusives des émulsions contenant des silicones, dont les valeurs étaient comparables à celles du contrôle négatif. Les émulsions à base de silicone ont obtenu des scores plus élevés chez les volontaires en termes de caractéristiques de douceur, de fraîcheur et de souplesse, tandis que des scores plus faibles ont été obtenus en termes d'onctuosité par rapport aux émulsions sans silicone. Aucun cas d'irritation n'a été enregistré chez les candidats. CONCLUSION: La présence de silicones spécifiques dans un produit cosmétique a amélioré ses caractéristiques technologiques. L'identité rhéologique et la caractéristique de stabilité ont montré la pertinence réelle d'une émulsion préparée en tant que produit cosmétique. De plus, cette étude a démontré que les émulsions à base de silicone sont sans danger pour la peau et n'ont provoqué aucune occlusion cutanée. Les consommateurs potentiels enregistrent une amélioration des sensations cutanées lorsque des silicones sont inclus dans la formulation.

Macrophage-Derived Extracellular Vesicles: A Promising Tool for Personalized Cancer Therapy.

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.

Ammonium Glycyrrhizinate and Bergamot Essential Oil Co-Loaded Ultradeformable Nanocarriers: An Effective Natural Nanomedicine for In Vivo Anti-Inflammatory Topical Therapies.

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.

Lyotropic Liquid Crystals: A Biocompatible and Safe Material for Local Cardiac Application.

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.

Multidrug Idebenone/Naproxen Co-loaded Aspasomes for Significant in†vivo Anti-inflammatory Activity.

The use of proper nanocarriers for dermal and transdermal delivery of anti-inflammatory drugs recently gained several attentions in the scientific community because they pass intact and accumulate payloads in the deepest layers of skin tissue. Ascorbyl palmitate-based vesicles (aspasomes) can be considered a promising nanocarrier for dermal and transdermal delivery due to their skin whitening properties and suitable delivery of payloads through the skin. The aim of this study was the synthesis of multidrug Idebenone/naproxen co-loaded aspasomes for the development of an effective anti-inflammatory nanomedicine. Aspasomes had suitable physicochemical properties and were safe in vivo if topically applied on human healthy volunteers. Idebenone/naproxen co-loaded aspasomes demonstrated an increased therapeutic efficacy of payloads compared to the commercially available Naprosyn® gel, with a rapid decrease of chemical-induced erythema on human volunteers. These promising results strongly suggested a potential application of Idebenone/naproxen multidrug aspasomes for the development of an effective skin anti-inflammatory therapy.

Rutin-Loaded Nanovesicles for Improved Stability and Enhanced Topical Efficacy of Natural Compound.

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.

EtoGel for Intra-Articular Drug Delivery: A New Challenge for Joint Diseases Treatment.

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.

Nanonutraceuticals: The New Frontier of Supplementary Food.

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.

Influence of Materials Properties on Bio-Physical Features and Effectiveness of 3D-Scaffolds for Periodontal Regeneration.

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.

Topical Unsaturated Fatty Acid Vesicles Improve Antioxidant Activity of Ammonium Glycyrrhizinate.

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.