Surfactant free synthesis of cationic nano-vesicles: A safe triple drug loaded vehicle for the topical treatment of cutaneous leishmaniasis.

The basic aim of the study was to develop and evaluate the triple drug loaded cationic nano-vesicles (cNVs), where miltefosine was used as a replacement of surfactant (apart from its anti-leishmanial role), in addition to meglumine antimoniate (MAM) and imiquimod (Imq), as a combination therapy for the topical treatment of cutaneous leishmaniasis (CL). The optimized formulation was nano-sized (86.2 ±â€¯2.7 nm) with high entrapment efficiency (63.8 ±â€¯2.1% (MAM) and 81.4 ±â€¯2.3% (Imq)). In-vivo skin irritation assay showed reduced irritation potential and a decrease in the cytotoxicity of cNVs as compared to conventional NVs (having sodium deoxycholate as a surfactant). A synergistic interaction between drugs was observed against intracellular amastigotes, whereas the in-vivo antileishmanial study presented a significant reduction in the parasitic burden. The results suggested the potential of surfactant free, triple drug loaded cNVs as an efficient vehicle for the safe topical treatment of CL.

Physicochemical Characterization and Skin Permeation of Cationic Transfersomes Containing the Synthetic Peptide PnPP-19.

BACKGROUND: PnPP-19 is a 19-amino-acid synthetic peptide previously described as a novel drug for the treatment of erectile dysfunction. OBJECTIVE: The aim of this work was to evaluate the physicochemical properties of cationic transfersomes containing PnPP-19 and the skin permeation of free PnPP-19 and PnPP-19-loaded transfersomes. METHODS: Three different liposomal preparation methods were evaluated. Cationic transfersomes contained egg phosphatidyl choline: stearylamine (9:1 w/w) and Tween 20 (84.6:15.4 lipid:Tween, w/w). Lipid concentration varied from 20 to 40 mM. We evaluated the entrapment percentage, mean diameter, zeta potential and stability at 4 °C of the formulations. The skin permeation assays were performed with abdominal human skin using Franz diffusion cell with 3 cm2 diffusion area at 32 °C and a fluorescent derivative of the peptide, containing 5-TAMRA, bound to PnPP-19 C-terminal region, where an extra lysine was inserted. RESULTS: Our results showed variable entrapment efficiencies, from 6% to 30%, depending on the preparation method and the lipid concentration used. The reverse phase evaporation method using a total lipid concentration equal to 40 mM led to the best entrapment percentage (30.2 + 4.5%). Free PnPP-19 was able to permeate skin at a rate of 10.8 ng/cm2/h. However, PnPP-19 was specifically hydrolyzed by skin proteases, generating a fragment of 15 amino acid residues. Encapsulated PnPP-19 permeated the skin at a rate of 19.8 ng/cm2/h. CONCLUSION: The encapsulation of PnPP-19 in cationic transfersomes protected the peptide from degradation, favoring its topical administration.