Formulation, characterization, and evaluation of in vitro skin permeation and in vivo pharmacodynamics of surface-charged tripterine-loaded nanostructured lipid carriers

Abstract

Yan Chen, Lei Zhou, Ling Yuan, Zhen-hai Zhang, Xuan Liu, Qingqing WuKey Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, ChinaBackground: Nanostructured lipid carriers (NLCs) are attractive materials for topical drug delivery, and in a previous study, we demonstrated that NLCs loaded with tripterine enhance its deposition. However, the surface charge of nanoparticles influences percutaneous drug penetration. Therefore, we aimed to evaluate the influence of the surface charge of NLCs on in vitro skin permeation and in vivo pharmacodynamics of tripterine and optimize tripterine-loaded NLCs for the treatment of skin diseases.Methods: Different solid and liquid matrices were selected to prepare cationic, anionic, and neutral NLCs by the solvent evaporation method. The in vitro studies were evaluated by using Franz diffusion cells. The effect of surface-charged NLCs on cellular uptake was appraised across HaCaT and B16BL6 cells. The in vitro and in vivo anticancer activity of surface-charged NLCs was evaluated in B16BL6 cells and melanoma-bearing mice, respectively.Results: The average particle sizes of the cationic, anionic, and neutral NLCs were 90.2 ± 9.7, 87.8 ± 7.4, and 84.5 ± 10.2 nm, respectively; their encapsulation efficiencies were 64.3% ± 5.1%, 67.8% ± 4.4%, and 72.5% ± 4.9%, respectively. In vitro studies showed delayed tripterine release, and the order of skin permeation was cationic NLCs > anionic NLCs > neutral NLCs. Further, in vitro cytotoxicity studies showed that the cationic NLCs had the highest (P < 0.05) inhibition ratio in B16BL6 (melanoma) cells. Moreover, in vivo pharmacodynamic experiments in melanoma-bearing mice indicated that the cationic NLCs had significantly higher (P < 0.05) antimelanoma efficacy than the anionic and neutral NLCs.Conclusion: The surface charge of NLCs has a great influence on the skin permeation and pharmacodynamics of tripterine. Cationic tripterine-loaded NLCs could enhance the percutaneous penetration and antimelanoma efficacy of tripterine and offer several advantages over tripterine alone. Therefore, they are promising carriers of tripterine for topical antimelanoma therapy.Keywords: surface charge, nanostructured lipid carriers, tripterine, percutaneous penetration, cellular uptake, antimelanoma efficacy