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

渗透 化学 色谱法 阳离子聚合 钙黄绿素 生物化学 有机化学
作者
Flávia De Marco Almeida,Carolina Nunes da Silva,Sávia Caldeira de Araújo Lopes,Daniel Moreira dos Santos,Fernanda Silva Torres,Felipe Lima Cardoso,Patrícia Massara Martinelli,Elizabeth Ribeiro da Silva,Maria Elena de Lima,Lucas Antonio Ferreira Miranda,Mônica Cristina Oliveira
出处
期刊:Current Drug Delivery [Bentham Science Publishers]
卷期号:15 (7): 1064-1071 被引量:11
标识
DOI:10.2174/1567201815666180108170206
摘要

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. Keywords: Cationic transfersomes, peptide, PnPP-19, skin permeation, topical delivery system, nanotechnology.
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