Ciclopirox and Efinaconazole Transungual Permeation, Antifungal Activity, and Proficiency To Induce Resistance in Trichophyton rubrum.

Onychomycosis is a nail fungal infection, mostly caused by dermatophytes. The treatment efficacy is impaired by difficulties of reaching effective drug levels at the site of infection; frequent relapses occur after cessation of antifungal therapy. The aim of the study was to compare two commercial products containing ciclopirox or efinaconazole for antimycotic activity and antifungal drug resistance. A study of permeation and penetration through bovine hoof membranes, as a nail model, was performed to evaluate the antimycotic activity of permeates against clinical isolates of selected fungi, and the frequency of spontaneous in vitroTrichophyton rubrum-resistant strains was assessed by broth microdilution assays. The results suggest that ciclopirox creates a depot in the nail, leading to a gradual release of the drug over time with action on both the nail plate and bed. Conversely, efinaconazole, mildly interacting with nail keratin, mainly exerts its antifungal activity in the nail bed. However, in the case of T. rubrum, the antifungal activities of the drugs in the nail plate seem comparable. Finally, efinaconazole showed a potential for induction of resistance in T. rubrum, which may limit its efficacy over time. Ciclopirox did not show any potential to induce resistance in T. rubrum and appears endowed with a more complete activity than efinaconazole in the management of onychomycosis as the nail keratin is a substrate for the growth of fungal cells, and the availability of drug in large concentration just in the nail bed may not be sufficient to guarantee the complete eradication of pathogens.

Diclofenac-Derived Hybrids for Treatment of Actinic Keratosis and Squamous Cell Carcinoma.

In this work, hybrid compounds 1-4 obtained by conjugation of the non-steroidal anti-inflammatory drug diclofenac, with natural molecules endowed with antioxidant and antiproliferative activity were prepared. The antiproliferative activity of these hybrids was evaluated on immortalized human keratinocyte (HaCaT) cells stimulated with epidermal growth factor (EGF), an actinic keratosis (AK) model, and on human squamous cell carcinoma (SCC) cells (A431). Hybrid 1 presented the best activity in both cell models. Self-assembling surfactant nanomicelles have been chosen as the carrier to drive the hybrid 1 into the skin; the in vitro permeation through and penetration into pig ear skin have been evaluated. Among the nanostructured formulations tested, Nano3Hybrid20 showed a higher tendency of the hybrid 1 to be retained in the skin rather than permeating it, with a desirable topical and non-systemic action. On these bases, hybrid 1 may represent an attractive lead scaffold for the development of new treatments for AK and SCC.

Effect of Tumor Relevant Acidic Environment in the Interaction of a N-hydroxyindole-2-Carboxylic Derivative with the Phospholipid Bilayer.

PURPOSE: The inhibitors of the human isoform 5 of lactate dehydrogenase (hLDH5) have attracted growing interest as efficient anti-cancer agents. In the present paper, the interactions between an efficient hLDH5 inhibitor (N-hydroxyindole-2-carboxylic derivative) and lipid bilayers based on dipalmitoylphosphatidylcholine (DPPC) were investigated. Additionally, since interstitial acidification plays a key role in tumor pathogenesis and tumor drug therapy, the effect of acidic pH was assessed and correlated to DPPC/drug interaction. METHODS: Four different techniques were used: differential scanning calorimetry, dynamic light scattering, UV-VIS second derivative spectrometry and attenuated total reflection Fourier transformed infrared spectroscopy. RESULTS: All techniques concur in highlighting a structural change of lipid assembly, susceptible both to pH change and to the presence of the antitumor compound. Lipid vesicles appeared more compact at the lower pH, since the thermal pre-transition from the lamellar gel phase to the ripple gel phase was absent at pH 7.4 and the infrared analysis revealed a stronger acyl chain packing as well as a different hydration degree. Drug interaction was mainly detected in the lipid region including the ester linkages and the first portion of the acyl chains. Furthermore, a lower drug partitioning was recorded at pH 6.6. CONCLUSIONS: The investigated antitumor agent possesses a stable negative charge at the investigated pH values, thus the lower interaction at the acidic pH is mainly ascribable to an environmental effect on lipid assembly. Therefore, drug efficacy under tumor acid conditions may be hampered by the observed lipid membrane constraints, and suggest for the development of suitable prodrugs.

A water-soluble, mucoadhesive quaternary ammonium chitosan-methyl-ß-cyclodextrin conjugate forming inclusion complexes with dexamethasone.

The ocular bioavailability of lipophilic drugs, such as dexamethasone, depends on both drug water solubility and mucoadhesion/permeation. Cyclodextrins and chitosan are frequently employed to either improve drug solubility or prolong drug contact onto mucosae, respectively. Although the covalent conjugation of cyclodextrin and chitosan brings to mucoadhesive drug complexes, their water solubility is restricted to acidic pHs. This paper describes a straightforward grafting of methyl-ß-cyclodextrin (MCD) on quaternary ammonium chitosan (QA-Ch60), mediated by hexamethylene diisocyanate. The resulting product is a water-soluble chitosan derivative, having a 10-atom long spacer between the quaternized chitosan and the cyclodextrin. The derivative is capable of complexing the model drug dexamethasone and stable complexes were also observed for the lyophilized products. Furthermore, the conjugate preserves the mucoadhesive properties typical of quaternized chitosan and its safety as solubilizing excipient for ophthalmic applications was preliminary assessed by in vitro cytotoxicity evaluations. Taken as a whole, the observed features appear promising for future processing of the developed product into 3D solid forms, such as controlled drug delivery systems, films or drug eluting medical devices.

Influence of a Combination of Chemical Enhancers and Iontophoresis on In Vitro Transungual Permeation of Nystatin.

To promote transungual permeation of nystatin (NYST), molecule with high molecular weight, no water-soluble, amphoteric by iontophoresis. The synergic effect of the combination of cetylpyridinium chloride, CPC, or polyoxyethylene (20) sorbitan monooleate, TW80, and iontophoresis was investigated. In vitro permeation experiments were carried out through bovine hoof slices using vertical diffusion cells. A low current density (0.2 mA/cm2) was applied by introducing Ag/AgCl electrodes in the donor (anode) and receptor (cathode) chambers. The donor phase consisted of a solution, a suspension, or gel-type vehicles containing NYST and surfactants in pH 5.6 HEPES buffer. The addition of CPC to NYST suspension (SOSP) produced a fivefold increase on the permeability of the bovine hoof membrane to the drug. The application of anodal iontophoresis further improved NYST flux. Conversely, NYST transungual permeation was not influenced by TW80 either in the passive diffusion or iontophoretic flux. Furthermore, the iontophoretic treatment does not appear to induce irreversible alterations to the hoof bovine membranes. The present work demonstrated the efficacy of iontophoresis as a treatment for different nail pathologies with large molecules very slightly soluble in water without irreversibly affecting the nail structure. A synergistic effect between CPC and iontophoresis was observed.

In vitro evaluation of some parameters involved in mucoadhesion of aqueous polymeric dispersions.

CONTEXT: The mucoadhesive formulations are constantly developing due to their relevance in the drug delivery to various districts of the organism. OBJECTIVE: The purpose of this study was to find a direct link between physicochemical properties of the polymers and their adhesive ability in order to offer guidelines for the development of mucoadhesive semisolid formulations. MATERIALS AND METHODS: Twelve polymers were dispersed in water and characterized with regard to their mucoadhesiveness, apparent viscosity, contact angle on solid surface, and hydrodynamic diameter of their molecules. The adhesive properties were related to the other measured parameters. RESULTS AND DISCUSSION: The data seem to indicate the existence of an optimal value of viscosity, around 5-6 Pa s, to obtain the highest mucoadhesiveness of the polymeric dispersions. Regarding the molecular sizes, the best mucoadhesive performances seem to be given from polymers with a hydrodynamic diameter lower than 350-400 nm. In any case, the ability to wet the surface by the polymeric dispersion seems to play an essential role in bioadhesion process, capable of strongly limiting the phenomenon. CONCLUSIONS: Performing simple in vitro measurements, it seems possible to identify the best polymeric concentration to obtain a semisolid formulation with good mucoadhesive properties.

Ciclopirox vs amorolfine: in vitro penetration into and permeation through human healthy nails of commercial nail lacquers.

One of the pre-requisite for a successful topical antifungal drug indicated for onychomycosis is its bioavailability into the nail unit for achieving fungal eradication and clinical benefit. The aim of this study was to compare in vitro permeation/penetration through and into human nails of amorolfine (MRF) from a 5% anhydrous commercial formulation (Loceryl®) and ciclopirox (CPX) from the 8% aqueous formulation in hydroxypropyl chitosan (HPCH) technology (Onytec®). The ability of the active ingredient to reach efficacious concentrations to inhibit nail pathogens was also evaluated. The amounts of drug permeated and retained in human healthy nails were determined using a suitably modified diffusion apparatus. HPLC analysis of the samples was performed. The HPCH-based CPX formulation demonstrated an efficient penetration into and permeation through the nail plates. Conversely, Loceryl® produced an amount of MRF permeated through and penetrated into the human toenails significantly lower than CPX. The evaluation of the efficacy index showed a higher potential efficacy of Onytec® with respect to Loceryl® on nail pathogens. The present work not only reinforced the previous results on different experimental substrates, but pointed out the superiority of HPCH-based Onytec® formulation containing CPX with respect to Loceryl® commercial product with MRF, both in terms of higher permeation through and penetration into the human nail, and for the efficacy towards the most common ungual pathogens.

Nanomicellar eye drops: a review of recent advances.

INTRODUCTION: Research on nanotechnology in medicine has also involved the ocular field and nanomicelles are among the applications developed. This approach is used to increase both the water solubility of hydrophobic drugs and their penetration/permeation within/through the ocular tissues since nanomicelles are able to encapsulate insoluble drug into their core and their small size allows them to penetrate and/or diffuse through the aqueous pores of ocular tissues. AREAS COVERED: The present review reports the most significant and recent literature on the use of nanomicelles, made up of both surfactants and amphiphilic polymers, to overcome limitations imposed by the physiology of the eye in achieving a high bioavailability of drugs intended for the therapeutic areas of greatest commercial interest: dry eye, inflammation, and glaucoma. EXPERT OPINION: The results of the numerous studies in this field are encouraging and demonstrate that nanomicelles may be the answer to some of the challenges of ocular therapy. In the future, new molecules self-assembling into micelles will be able to meet the regulatory requirements for marketing authorization for their use in ophthalmic formulations.

Binary Polymeric Surfactant Mixtures for the Development of Novel Loteprednol Etabonate Nanomicellar Eyedrops.

The treatment of several ocular inflammatory conditions affecting different areas of the ocular globe involves the administration of topical ophthalmic formulations containing corticosteroids. This research was aimed at evaluating the solubilising efficacy of 5.0% w/w of different binary mixtures of commercial amphiphilic polymeric surfactants with the purpose of obtaining nanomicellar solutions containing a high amount of loteprednol etabonate (LE). The selected LE-TPGS/HS nanomicelles, containing 0.253 mg/mL of the drug, had a small size (=13.57 nm) and uniform distribution (Polydispersity Index = 0.271), appeared completely transparent and perfectly filterable through 0.2 µm membrane filter, and remained stable up to 30 days at 4 °C. The critical micellar concentration (CMCTPGS/HS) was 0.0983 mM and the negative value of the interaction parameter between the polymeric-surfactant-building unit (ßTPGS/HS = -0.1322) confirmed the ability of the polymeric surfactants to interact, favouring the dissolution of LE into nanomicelles. The disappearance of the endothermic peak of LE in the DSC analysis confirmed the interactions of LE with the polymeric surfactants. LE-TPGS/HS produced in vitro LE which sustained diffusion for 44 h (more than 40% of encapsulated LE). Furthermore, the lack of a significant cytotoxic effect on a sensitive corneal epithelial cell line makes it a candidate for further biological studies.

Nanostructured Drug Delivery Systems for Targeting 5-α-Reductase Inhibitors to the Hair Follicle.

Androgenetic alopecia is a multifactorial condition characterized by noticeable hair loss, affecting both men and women and representing a debilitating and chronic disorder that considerably affects the quality of life. Available topical treatments based on minoxidil or finasteride require repeated applications and are associated with a certain number of adverse effects. The challenges associated with current treatments pave the way for the research of new therapeutic strategies, more precise and selective, and capable of providing long-term results. In this context, the present review examines the new proposed formulation strategies to deliver 5-α-reductase inhibitors in order to obtain a targeted drug delivery, for improving drug retention at the site of action in the hair follicle, contemporaneously reducing drug systemic absorption, which is the cause of important adverse effects. In particular, the research will be focused on the several aspects that influence the performance of nanostructured drug delivery systems in creating a depot in the hair follicles, such as particle size, surface charge, excipients, and combined application with external stimuli (infrared radiation, mechanical massage, ultrasounds application).

Hydrogels as Corneal Stroma Substitutes for In Vitro Evaluation of Drug Ocular Permeation.

Hydrogels are complex hydrophilic structures, consisting of crosslinked homopolymers or copolymers insoluble in water. Due to their controllable bio-physicochemical properties mimicking the morphology of the native extracellular matrix, they are a key part of a lot of research fields, including medicine, pharmaceutics, and tissue engineering. This paper was focused on the preparation and characterization of hydrogels from different blends of polyvinyl alcohol (PVA) with microcrystalline cellulose (MCC) and gelatin (GEL) at various ratios, and from gelatin and chitosan alone to understand their feasibility of utilizing as corneal stroma substitutes in permeability tests for drug candidate molecules in early stages of their development. The characterization was carried out by differential scanning calorimetry, electron microscopy (SEM), water content, mass loss, water permeability, wettability, and tensile stress-strain tests. After the physicochemical characterization, PVA/MCC blend and chitosan proved to be the most promising constructs, showing negligible mass loss after immersion in aqueous medium for two weeks and low hydrodynamic permeability. They were then employed in drug molecules permeation studies and these data were compared to that obtained through excised tissues. The results obtained showed that PVA/MCC hydrogels have similar mechanical and permeability properties to corneal stroma.

Ciclopirox Hydroxypropyl Chitosan (CPX-HPCH) Nail Lacquer and Breathable Cosmetic Nail Polish: In Vitro Evaluation of Drug Transungual Permeation Following the Combined Application.

BACKGROUND: Onychomycosis produces nail chromatic alterations that lead patients to mask them with cosmetic enamels. Objectives: Evaluate drug transungual permeation and antimycotic activity against selected strains after application of CPX-HPCH nail lacquer (NL) on the nail pre-covered with breathable cosmetic polish. METHODS: CPX transungual permeation after applying CPX-HPCH NL once or twice a day on bovine hoof membranes pre-covered with a breathable cosmetic nail polish was compared to that obtained applying CPX-HPCH NL directly on the membrane. The relevant experimental permeates underwent an in vitro susceptibility test. RESULTS: After CPX-HPCH NL application once a day, the drug transungual flux in the presence of cosmetic product tended to decrease while maintaining the antifungal activity. Two daily applications of CPX-HPCH NL on the membrane pre-covered with cosmetic polish exhibited the same permeation profile as daily application of the medicated lacquer directly on the nail as well as the same microbiological activity. CONCLUSIONS: The breathable cosmetic nail polish can be applied on the nail affected by onychomycosis in association with CPX-HPCH NL to mask the imperfections. The application of CPX-HPCH NL twice a day appears to be a good solution to obtain the same results as for a daily application without the presence of the cosmetic layer.

MAGL inhibitor NanoMicellar formulation (MAGL-NanoMicellar) for the development of an antiglaucoma eye drop.

The ocular endocannabinoid system (ECS) including enzymes and CB1/CB2 receptors determines various substantial effects, such as anti-inflammatory activity and reduction of the intraocular pressure (IOP). The modulation of 2-arachidonoylglycerol (2-AG) levels obtained via MAGL inhibition is considered as a promising pharmacological strategy to activate the ECS. Within the scope of this study, the effect of a selective monoacylglycerol lipase (MAGL) inhibitor (MAGL17b) was investigated by measuring the IOP reduction in normotensive rabbits after performing a solubilisation process of the molecule with non-ionic surfactants, to produce suitable eye drops containing the highest possible concentration of the drug. Furthermore, the study involved the evaluation of cytotoxicity and of in vitro/ex vivo corneal permeation of MAG17b of selected formulations based on polyoxyl(35)castor oil (C-EL) and polyethylene glycol (80) sorbitan monolaurate (TW80). The solubilisation of 0.5 mM MAGL17b with 3 % w/w TW80 (TW80/3-17b), through the formation of NanoMicellar structures (diameter of 12.3 nm), determined a significant permeation of MAGL17b, both through excised rabbits corneas and reconstituted corneal epithelium, with a limited corneal epithelial cells death. The blockade of MAGL activity induced a IOP reduction up to 4 mmHg in albino and pigmented rabbits after topical instillation, thus confirming the potential efficacy of the MAGL inhibition approach in the treatment of ocular pathologies.

Sporopollenin Microcapsule: Sunscreen Delivery System with Photoprotective Properties.

In recent years, the demand for high-quality solar products that combine high efficacy with environmentally friendly characteristics has increased. Among the coral-safe sunscreens, ethylhexyl triazone (Uvinul® T150) is an effective organic UVB filter, photostable and practically insoluble in water, therefore difficult to be formulated in water-based products. Oil-free sunscreens are considered ideal for most skin types, as they are not comedogenic and do not leave the skin feeling greasy. Recent studies reported that pollen grains might represent innovative drug delivery systems for their ability to encapsulate and release active ingredients in a controlled manner. Before being used, the pollen grains must be treated to remove cellular material and biomolecules, which could cause allergic reactions in predisposed subjects; the obtained hollow structures possess uniform diameter and a rigid wall with openings that allow them to be filled with bioactive substances. In the present work, pollen from Lycopodium clavatum has been investigated both as a delivery system for ethylhexyl triazone and as an active ingredient by evaluating its photoprotective capacity. The goal is to obtain environmentally friendly solar aqueous formulations that take advantage of both sunscreen and sporopollenin microcapsules' UV protection with a relatively low cost, as these pollen grains are widely available.

Permeation and distribution of ferulic acid and its α-cyclodextrin complex from different formulations in hairless rat skin.

Ferulic acid (FA) is a natural product that occurs in seeds of many plants where it is generally located in the bran. This compound is a multifunctional ingredient endowed with antioxidative, radical scavenging, sunscreening and antibacterial actions. The aim of this study was to analyse the ferulic acid cutaneous permeation and distribution, through and into the skin layers, from different cosmetic vehicles, an O/W emulsion (pH 6.0) and two gel-type formulations at different pH levels (6.0 and 7.4), containing FA alone or an inclusion complex with α-cyclodextrin (CD-FA). In vitro permeation studies were performed in vertical diffusion cells using hairless rat excised skin. At appropriate intervals of time, the amount of permeated sunscreen/radical scavenger was evaluated by high-performance liquid chromatography (HPLC). At the end of experiments, treated skin samples were sectioned with a cryomicrotome and the FA content of the individual slices was analysed by HPLC. FA-containing formulations, O/W emulsion, gels A and B, originated FA fluxes of 8.48 ± 2.31, 8.38 ± 0.89 and 5.72 ± 0.50 µg/cm(2) h, respectively, thus suggesting the pH influence on FA percutaneous permeation. The use of the inclusion complex, CD-FA, determined in all cases a decrease of FA transdermal permeation while no influence of pH was observed. Gel-type formulations containing FA ensured higher sunscreen storage in the superficial layers if compared with O/W emulsion. When FA was included in α-cyclodextrin, FA amount retained into skin layers decreased markedly.

Combination of Nanomicellar Technology and In Situ Gelling Polymer as Ocular Drug Delivery System (ODDS) for Cyclosporine-A.

A combination of in situ gelling systems and a loaded drug self-assembling nanomicellar carrier was chosen in this study as a new potential Ocular Drug Delivery System (ODDS) for Cyclosporine-A (CyA), a poorly water-soluble drug. Two non-ionic surfactants (d-α-tocopherol polyethylene glycol succinate, VitE-TPGS and polyoxyl 40 hydrogenated castor oil, RH-40) were used to produce the nanomicelles. The physical-chemical characterization of the nanomicelles in terms of CyA entrapment (EE%) and loading efficiency (LE%), cloud point (CP), regeneration time (RT), size and polydispersity index (PI) allowed us to select the best combination of surfactant mixture, which showed appropriate stability, high CyA-EE (99.07%), very small and homogeneous dimensions and favored the solubilization of an amount of CyA (0.144% w/w) comparable to that contained in marketed emulsion Ikervis®. The selected nanomicellar formulation incorporated into optimized ion-sensitive polymeric dispersions of gellan gum (GG-LA: 0.10, 0.15 and 0.20% w/w) able to trigger the sol-gel transition after instillation was characterized from technological (osmolality, pH, gelling capacity, rheological behavior, wettability, TEM and storage stability at 4 and 20 °C) and biopharmaceutical points of view. This new combined approach allowed us to obtain clear aqueous dispersions that were easy to instill and able to form a viscous gel when in contact with the tear fluid, improving CyA ocular bioavailability. Furthermore, this new ODDS prevented CyA transcorneal permeation, exhibited low cytotoxicity and prolonged the CyA resident time in the precorneal area compared to Ikervis®.

Ocular Application of Oleuropein in Dry Eye Treatment: Formulation Studies and Biological Evaluation.

BACKGROUND: Oleuropein is already known for its numerous pharmacological properties, but its activity in the ocular field has not yet been investigated. The study aims to verify a possible use of oleuropein (OLE)-based eye drops both in terms of efficacy in dry eye syndrome and stability in aqueous solution. METHODS: OLE was co-precipitated with HP-ß-cyclodextrin, and the obtained complex was encapsulated into liposomes prepared by hydration of a lipid film composed of Lipoid S100 and cholesterol with different pH buffer solutions. The hydrated vesicles were shrunk by ultrasonication or extrusion. The preparations were characterized from the physicochemical point of view by subjecting them to differential scanning calorimetry, ATR-FTIR, dynamic light scattering analysis, and microscopy. Subsequently, OLE protective activity against hyperosmotic and oxidative stress on rabbit corneal epithelial cells (RCE) was evaluated. RESULTS: The liposomal vesicles obtained after extrusion showed a tendency towards greater encapsulation efficiency (up to 80.77%) compared to that obtained by sonication, and the liposomes hydrated in pH 5.5 solution tended to incapsulate more than the neutral ones. Ultrasonication produced two-dimensional populations of liposomes, the largest of which reached 2149 nm. On the contrary, the extruded liposomes showed homogeneous diameters of about 250 nm. Complexation with cyclodextrin and subsequent encapsulation in liposomes greatly increased the OLE stability in aqueous solution, especially at 4 °C and for the extruded formulations. OLE aqueous solution (OLE7.4-sol, reference) and neutral extruded liposomes (F7.4-e) were well tolerated on RCE cells. Moreover, OLE was able to control the effects of hyperosmolarity on ocular surface cells and to prevent oxidative stress-induced loss of cell viability.

A hybrid ocular delivery system of cyclosporine-A comprising nanomicelle-laden polymeric inserts with improved efficacy and tolerability.

We report on hybrid nanomicelle-polymer inserts for improved delivery of cyclosporine A (CyA) to the surface of the eye. Hybrid inserts containing a nanomicellar formulation were prepared by the solvent casting method; their characteristics, in vitro release of CyA, eye irritation potential, nanomicelle distribution inside the insert, and in vivo pharmacokinetics of the most promising solid formulation (F3) were investigated. Nanomicelles capable of accommodating a therapeutically relevant amount of CyA (57.22 ± 5.90-68.52 ± 1.4 µg) were incorporated into five different polymeric formulations (F1-F5). The developed inserts displayed promising characteristics (size, weight, surface pH, and contact angle) that fulfill ocular tolerability requirements. Considering the technological properties and CyA in vitro release, F3 and F5 were the most promising formulations. SEM analysis suggested the F3 formulation as the potential prototype for CyA ocular delivery. The F3 formulation (CyA: 60.08 ± 2.85 µg) did not induce conjunctival irritation when HET-CAM assay was performed and was hence considered suitable for further study in a rabbit eye. The AUC value for CyA loaded in the F3 insert was about 2-fold greater than that obtained with the Ikervis® used as a control formulation. F3 produced a significant reduction (of about 7-folds) in the rate of CyA elimination from the tear fluid relative to Ikervis® and about 4-fold greater reduction than Nano-CyA (p = 0.0187). The ability of F3 to delay the elimination of the drug from the precorneal area is particularly desirable when treating dry eye syndrome. Furthermore, F3 did not induce ocular discomfort, a typical characteristic of solid ocular inserts, including commercially available ones.

Tyrosol-Enriched Tomatoes by Diffusion across the Fruit Peel from a Chitosan Coating: A Proposal of Functional Food.

Chitosan is receiving increasing attention from the food industry for being a biodegradable, non-toxic, antimicrobial biopolymer able to extend the shelf life of, and preserve the quality of, fresh food. However, few studies have investigated the ability of chitosan-based coatings to allow the diffusion of bioactive compounds into the food matrix to improve its nutraceutical quality. This research is aimed at testing whether a hydrophilic molecule (tyrosol) could diffuse from the chitosan-tyrosol coating and cross the tomato peel. To this end, in vitro permeation tests using excised tomato peel and an in vivo application of chitosan-tyrosol coating on tomato fruit, followed by tyrosol quantification in intact fruit, peel and flesh during a seven-day storage at room temperature, were performed. Both approaches demonstrated the ability of tyrosol to permeate across the fruit peel. Along with a decreased tyrosol content in the peel, its concentration within the flesh was increased, indicating an active transfer of tyrosol into this tissue. This finding, together with the maintenance of constant tyrosol levels during the seven-day storage period, is very promising for the use of chitosan formulations to produce functional tomato fruit.

Formulations Based on Natural Ingredients for the Treatment of Nail Diseases.

Nail is a strong and resistant structure, characterized by a low permeability to foreign molecules. Nails can be subjected to many diseases, among which fungal infections (e.g. onchomycosis) are the most common and responsible for nail structure alteration. Many formulations have been produced for the delivery of active ingredients to treat nail disorders, based on newly synthesized active molecules or containing chemical enhancers or chemically-modified polymers able to improve the drug transungual penetration. To avoid permanent alterations of the nail structure due to the use of chemical compounds or organic solvent-based formulation, researchers have developed novel formulations focusing on the use of new natural-based compounds. The purpose of this review is to provide information on the outcoming of natural ingredients-based formulations that have been developed in the last years as potential alternative to chemical-based formulations.