In Vitro and In Vivo Skin Distribution of 5α-Reductase Inhibitors Loaded Into Liquid Crystalline Nanoparticles

In this study, we developed positively charged liquid crystalline nanoparticles (LCN) coated with chitosan (CHI) to enhance the skin permeation and distribution of 5 alpha-reductase inhibitors for the treatment of androgenetic alopecia. LCN and surface-modified LCN (CHI-LCN) were prepared by ultrasonication method, and their physicochemical properties were characterized. In vitro and in vivo skin permeation and retention were studied using porcine abdominal skin and mice skin using the Franz diffusion cell. Skin distribution and cellular uptake of LCN and CHI-LCN were also investigated. The particle size and surface charge were 244.9 +/- 2.1 nm and -19.2 +/- 1.1 mV, respectively, for LCNs and 300.0 +/- 7.6 nm and 24.7 +/- 2.4 mV, respectively, for CHI-LCN. The permeation of 5 alpha-reductase inhibitors was significantly greater with CHI-LCN compared with LCN, whereas there was no significant difference observed in the skin distribution. In fluorescence studies, fluorescence intensity was higher for CHI-LCNs throughout the skin, whereas more intense fluorescence was seen only in the epidermis layer for LCN. CHI-LCN showed greater cellular uptake than LCN, resulting in internalization of 98.5 +/- 1.9% of nanoparticles into human keratinocyte cells. In conclusion, surface modification of LCN with CHI is a promising strategy for increasing skin permeation of 5 alpha-reductase inhibitors for topical delivery. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.