Squalene-containing nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of diphencyprone for treating alopecia areata.
OBJECTIVE
Diphencyprone (DPCP) is a therapeutic agent for treating alopecia areata. To improve skin absorption and follicular targeting nanostructured lipid carriers (NLCs) were developed.


METHODS
Nanoparticles were characterized by size, zeta potential, molecular environment, differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). In vitro and in vivo skin absorption experiments were performed. Fluorescence and confocal microscopes for imaging skin distribution were used.


RESULTS
NLCs with different designs were 208 ~ 265 nm with  > 77% DPCP encapsulation. NLCs incorporating a cationic surfactant or more soybean phosphatidylcholine (SPC) showed higher lipophilicity compared to typical NLCs by Nile red emission. All NLCs tested revealed controlled DPCP release; burst release was observed for control. The formulation with more SPC provided 275 μg/g DPCP skin retention, which was greater than control and other NLCs. Intersubject deviation was reduced after DPCP loading into NLCs. Cyanoacrylate skin biopsy demonstrated greater follicular deposition for NLCs with more SPC compared to control. Cationic NLCs but not typical or SPC-containing carriers were largely internalized into keratinocytes. In vivo skin retention of NLCs with more SPC was higher than free control. Confocal imaging confirmed localization of NLCs in follicles and intercellular lipids of stratum corneum.


CONCLUSIONS
This work encourages further investigation of DPCP absorption using NLCs with a specific formulation design.
School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Yin-Ku
YK
Lin
Saleh A
SA
Al-Suwayeh
Yann-Lii
YL
Leu
Feng-Ming
FM
Shen
Jia-You
JY
Fang
D000506:Alopecia Areata / Q000188:drug therapy*; D000818:Animals; D003521:Cyclopropanes / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D018859:Hair Follicle / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000648:ultrastructure; D012869:Skin Absorption; D013185:Squalene / Q000737:chemistry* / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism
D003521:Cyclopropanes; D003692:Delayed-Action Preparations; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D013185:Squalene; C029402:diphenylcyclopropenone