Nanomedicines to Treat Skin Pathologies with Natural Molecules.

The skin and mucous membranes are subjected to many disorders and pathological conditions. Nature offers a wide range of molecules with antioxidant activity able to neutralize, at least in part, the formation of free radicals and therefore to counteract the phenomena of cellular aging. Since synthetic drugs for the treatment of skin diseases can induce resistance, it is particularly interesting to use compounds of plant origin, transporting them in pharmaceutical forms capable of controlling their release and absorption. This review provides an overview of new findings about the use of lipid-based nanosystems for the delivery of natural molecules useful on the topical treatment of skin disorders. Several natural molecules encapsulated in lipid nanosystems have been considered in the treatment of some skin pathologies or diseases. Particularly, the use of rosemary and eucalyptus essential oil, saffron derivatives, curcumin, eugenol, capsaicin, thymol and lycopene has been reported. The molecules have been alternatively encapsulated in viscous systems, such as the organogels, or in liquid systems, such as ethosomes, transferosomes, solid lipid nanoparticles and monoolein based dispersions thickened by inclusion in carbomer gels. The nanostructured forms have been in vitro and in vivo investigated for the treatment of skin disorders due to dehydration, inflammation, melanoma, wound healing, fungal infections or psoriasis. The data reported in the different studies have suggested that the cutaneous application of lipid nanosystems allows a deep interaction between lipid matrix and skin strata, promoting a prolonged release and efficacy of the loaded natural molecules. This review suggests that the application of natural molecules onto the skin by lipid-based nanosystems can provide numerous clinician benefits in dermatology and cosmetics.

Cubic Phases, Cubosomes and Ethosomes for Cutaneous Application.

Cutaneous administration represents a good strategy to treat skin diseases, avoiding side effects related to systemic administration. Apart from conventional therapy, based on the use of semi-solid formulation such as gel, ointments and creams, recently the use of specialized delivery systems based on lipid has been taken hold. This review provides an overview about the use of cubic phases, cubosomes and ethosomes, as lipid systems recently proposed to treat skin pathologies. In addition in the final part of the review cubic phases, cubosomes and ethosomes are compared to solid lipid nanoparticles and lecithin organogel with respect to their potential as delivery systems for cutaneous application. It has been reported that lipid nanosystems are able to dissolve and deliver active molecules in a controlled fashion, thereby improving their bioavailability and reducing side-effects. Particularly lipid matrixes are characterized by skin affinity and biocompatibility allowing their application on skin. Indeed, after cutaneous administration, the lipid matrix of cubic phases and cubosomes coalesces with the lipids of the stratum comeum and leads to the formation of a lipid depot from which the drug associated to the nanosystem can be released in the deeper skin strata in a controlled manner. Ethosomes are characterized by a malleable structure that promotes their interaction with skin, improving their potential as skin delivery systems with respect to liposomes. Also in the case of solid lipid nanoparticles it has been suggested a deep interaction between lipid matrix and skin strata that endorses sustained and prolonged drug release. Concerning lecithin organogel, the peculiar structure of this system, where lecithin exerts a penetration enhancer role, allows a deep interaction with skin strata, promoting the transdermal absorption of the encapsulated drugs.

Hydrogel blends with adjustable properties as patches for transdermal delivery.

The effect of different preparation parameters were analyzed with respect to the rheological and pharmaceutical characteristics of hydrogel blend patches, as transdermal delivery formulation. Mixtures of pectin and gelatin were employed for the production of patches, with adjustable properties, following a two-step gelation procedure. The first gelation, a thermal one, is trigged by the presence of gelatin, whereas, the second gelation, an ionic one, is due to the formation of the typical egg box structure of pectin. In particular, the patch structural properties were assessed by oscillation stress sweep measurements which provided information concerning their viscolelastic properties. In addition, different modalities for drug loading were analyzed with respect to drug homogeneous distribution; testosterone was employed as model drug for transdermal administration. Finally, the performances of the produced transdermal patches were studied, in term of reproducibility and reliability, by determination of in vitro drug release profiles.

Effect of charge and lipid concentration on in-vivo percutaneous absorption of methyl nicotinate from liposomal vesicles.

We have investigated the influence of charge and lipid concentration on the in-vivo percutaneous absorption of a model compound, methyl nicotinate (MN), from liposomal vesicles. MN-loaded liposomes were produced by the reverse-phase evaporation method (REV) using different concentrations of phosphatidyl choline (PC), in association with surfactants such as dioctadecyl dimethyl ammonium bromide (DDAB18) and dicetyl phosphate (DCP), which impart a positive or negative charge to the systems, respectively. The liposomal suspensions were then processed to hydrogels and used to study in-vivo the MN permeation profile. MN was chosen as the model compound since it was capable of causing cutaneous erythema, the intensity and duration of which was proportional to the amount entering the living epidermis over time. The extent of the erythema was monitored by reflectance spectrophotometry, a non-invasive technique. In-vivo findings showed an interesting MN delayed release, which was proportional to the amount of phospholipids in each liposomal formulation. Furthermore, it could be noted that the erythematous effect was more prolonged when MN was delivered from neutral or negatively-charged liposomal forms.