Clobetasol-loaded nanostructured lipid carriers for epidermal targeting.

OBJECTIVES: The aim of this study was to investigate in vitro the epidermal targeting potential of clobetasol propionate-loaded nanostructured lipid carriers (CP-NLC) when compared to that of chitosan-coated (CP-NLC-C). METHODS: CP-NLC were prepared by microemulsion method and characterized by dynamic light scattering, transmission electron microscopy, in vitro release and permeation studies. To verify epidermal targeting, permeation studies were performed in two sets of experiments. For the first set, the skin was removed from the diffusion cell and stratum corneum (SC) was separated from the remaining skin (RS). For the second set, the whole epidermis (EP) was separated from the dermis (DER). CP quantification was performed in each skin layer. KEY FINDINGS: A novel clobetasol propionate-loaded NLC was produced with 1/5th of the drug dose used in commercial formulations and, even so, presented greater skin permeation. Both chitosan-coated and uncoated NLC enhanced the amount of CP in the epidermis more than 80-fold when compared to the commercial formulation (20.26 ± 2.77; 17.85 ± 0.49 and 0.22 ± 0.02 µg/cm(2) , respectively). Differently from chitosan-coated NLC, the uncoated NLC did not show dermal retention. CONCLUSIONS: NLC proved to be a system with potential for targeting drug delivery to the epidermal layer.

Liposomal voriconazole (VOR) formulation for improved ocular delivery.

Treating infectious eye diseases topically requires a drug delivery system capable of overcoming the eye's defense mechanisms, which efficiently reduce the drug residence time right after its administration, therefore reducing absorption. In order to try to surpass such administration issues and improve life quality for patients with fungal keratitis, liposomal voriconazol (VOR) formulations were prepared. Formulations were composed of soy phosphatidylcholine (PC) containing or not 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and cholesterol. Liposomes were characterized by their drug entrapment efficiency (EE), drug recovery (DR), average diameter (size) and polydispersivity index (PdI). In vitro mucosal interaction and irritancy levels, ex vivo permeation, as well as the short-term stability were also assessed. Liposomal VOR formulation produced with 7.2:40mM VOR:PC showed to be the most promising formulation: mean size of 116.6±5.9nm, narrow PdI (0.17±0.06), negative zeta potential (∼-7mV) and over 80% of EE and yield, remaining stable for at least 30 days in solution and 90 days after lyophilization. This formulation was classified as 'non-irritant' after HET-CAM's test and was able to deliver about 47.85±5.72µg/cm(2) of VOR into porcine cornea after 30min of permeation test. Such drug levels are higher than the minimal inhibitory concentrations (MIC) of several fungi species isolated from clinical cases of corneal keratitis. Overall results suggest VOR can be effectively incorporated in liposomes for potential topical treatment of fungal keratitis.