In vitro antifungal activity of polymeric nanoparticles loaded with Euphorbia tirucalli extract.

The therapeutic potential of medicinal plants is known as an alternative in treatment of human affections; in effect, the conventional application of these medicinal sources has several limitations like low bioavailability, solubility and stability, which affect its pharmacological efficacy. In recent decades, extraordinary advances have been made in new drug delivery systems using nanocarriers. This work consisted in determining the in vitro antifungal activity of the methanolic extract of Euphorbia tirucalli formulated in polymeric nanoparticles. The antifungal activity was determined by the microdilution method in 96-well microplates, applying nanoparticles loaded with plant extract (NP-Ext) obtained by nanoprecipitation on clinical isolates of Trichophyton rubrum and T. interdigitalis. Regarding the nanoparticles, the lots used did not present significant differences in their physicochemical characteristics, with a size of 91.885 ± 1.621nm, polydispersity index of 0.152 ± 0.025 and Z-potential of -6.047 ± 0.987. The quantification of the extract in the polymeric matrix was determined by infrared spectroscopy (FTIR), where an efficiency and encapsulation percentage of 22.15 ± 0.82 and 2.95 ± 0.11, respectively, were obtained. The in vitro antifungal activity of the crude and formulated extract was obtained calculating the Minimum Inhibitory Concentration (MIC) of each one; a MIC of 125 µg/mL was obtained against T. rubrum and T. interdigitalis with the crude extract, while a MIC value of 55.55 and 0.1 µg/mL was obtained with NP-Ext, respectively, against these same. Conclusions: biological activity is closely linked to the phytochemical profile of the extract; while the improvement of said potential with the NP-Ext with the dosage form was directly related to the physicochemical characteristics of the nanocarrier.

Skin penetration and distribution of polymeric nanoparticles.

Encapsulation using nanoparticulate systems is an increasingly implemented strategy in drug targeting and delivery. Such systems have also been proposed for topical administration to enhance percutaneous transport into and across the skin barrier. However, the mechanism by which such particulate formulations facilitate skin transport remains ambiguous. In this study, confocal laser scanning microscopy (CLSM) was used to visualize the distribution of non-biodegradable, fluorescent, polystyrene nanoparticles (diameters 20 and 200 nm) across porcine skin. The surface images revealed that (i) polystyrene nanoparticles accumulated preferentially in the follicular openings, (ii) this distribution increased in a time-dependent manner, and (iii) the follicular localization was favoured by the smaller particle size. Apart from follicular uptake, localization of nanoparticles in skin "furrows" was apparent from the surface images. However, cross-sectional images revealed that these non-follicular structures did not offer an alternative penetration pathway for the polymer vectors, whose transport was clearly impeded by the stratum corneum.

Visualization of skin penetration using confocal laser scanning microscopy.

The use of skin as an alternative route for administering systemically active drugs has attracted considerable interest in recent years. However, the skin provides an excellent barrier, which limits the number of drug molecules suitable for transdermal delivery. Thus, in order to improve cutaneous delivery, it is necessary to adopt an enhancement method, either (i) passively using novel formulations, e.g. microemulsions, liposomes, and colloidal polymeric suspensions, or more conventional skin permeation enhancers, or (ii) with a physical approach, such as, iontophoresis, sonophoresis or electroporation. Although there has been much progress, the precise modes of action of the different techniques used are far from well-understood. The objective of this review, therefore, is to evaluate how confocal laser scanning microscopy may contribute to the determination of the mechanisms of diverse skin penetration enhancement strategies.

Skin permeability enhancement by low frequency sonophoresis: lipid extraction and transport pathways.

The objective of this study was to shed light on the mechanism(s) by which low-frequency ultrasound (20 KHz) enhances the permeability of the skin. The physical effects on the barrier and the transport pathway, in particular, were examined. The amount of lipid removed from the intercellular domains of the stratum corneum following sonophoresis was determined by infrared spectroscopy. Transport of the fluorescent probes nile red and calcein, under the influence of ultrasound, was evaluated by laser-scanning confocal microscopy. The results were compared with the appropriate passive control data and with data obtained from experiments in which the skin was exposed simply to the thermal effects induced by ultrasound treatment. A significant fraction ( approximately 30%) of the intercellular lipids of the stratum corneum, which are principally responsible for skin barrier function, were removed during the application of low-frequency sonophoresis. Although the confocal images from the nile red experiments were not particularly informative, ultrasound clearly and significantly (again, relative to the corresponding controls) facilitated transport of the hydrophilic calcein via discrete permeabilized regions, whereas other areas of the barrier were apparently unaffected. Lipid removal from the stratum corneum is implicated as a factor contributing the observed permeation enhancement effects of low-frequency ultrasound. However, microscopic observations imply that sonophoresis induces localized (aqueous?) permeation pathways at discrete sites.

Biodegradable polymer nanocapsules containing a sunscreen agent: preparation and photoprotection.

Biodegradable polymer nanocapsules containing the lipophilic sunscreen, Parsol MCX (OMC), as the oil core were prepared by solvent displacement. We investigated the influence of polysorbate 85 (P-85) and poloxamer 188 (P-188) as stabilizing agents, the OMC loading capacity and the photoprotective potential of the formulations. The formation of nanocapsules is probably due to an interfacial instability arising from rapid diffusion of the solvent across the interface. The effectiveness of the stabilizing agents was attributed to their ability to inhibit coalescence during solvent diffusion. P-85 was a better stabilizer of poly(epsilon-Caprolactone)-nanocapsules than P-188. The OMC loading capacity was high (99+/-1% of OMC initial concentration). The in vitro release of OMC-nanocapsules is governed by hydrophobicity and crystallinity of the polymer and by the high lipophilicity of the drug. The OMC-nanocapsules provided partial protection against UV-induced erythema, in a manner significantly better than a conventional gel.