International Journal of Nanomedicine (Apr 2019)
Microemulsions vs chitosan derivative-coated microemulsions for dermal delivery of 8-methoxypsoralen
Abstract
Jun-Yong Wu,1–3,* Yong-Jiang Li,1–3,* Ting-Ting Liu,1–3 Ge Ou,1–3 Xiong-Bin Hu,1–3 Tian-Tian Tang,1–3 Jie-Min Wang,1–3 Xin-Yi Liu,1–3 Da-Xiong Xiang1–3 1Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People’s Republic of China; 2Institute of Clinical Pharmacy, Central South University, Changsha, Hunan 410011, People’s Republic of China; 3Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drugs, Changsha, Hunan, People’s Republic of China *These authors contributed equally to this work Background: 8-methoxypsoralen (8-MOP) is one of the most commonly utilized drugs in psoralen-ultraviolet A therapy for treatment of vitiligo. However, poor skin retention and systemic side effects limit the clinical application of 8-MOP. Methods: Microemulsions (MEs) and chitosan derivative-coated 8-MOP MEs were developed and compared for dermal delivery of 8-MOP. Ex vivo skin retention/permeation study was performed to select the ME formulation with the highest retention:permeation ratio. Four different chitosan-coated MEs were prepared and compared with the ME formulation for their ability to distribute 8-MOP in the skin.Results: Among various ME formulations developed, a formulation containing 2.9% ethyl oleate, 17.2% Cromophor EL35, 8.6% ethanol and 71.3% water showed the highest ex vivo skin retention:permeation ratio (1.98). Of four chitosan-coated MEs prepared, carboxymethyl chitosan-coated MEs (CC-MEs) and hydroxypropyl chitosan-coated MEs (HC-MEs) showed higher ex vivo skin retention:permeation ratio (1.46 and 1.84). and were selected for in vivo pharmacokinetic study. AUCskin (0–12 h) for 8-MOP MEs (4578.56 h·ng·mL-1) was higher than HC-MEs (3422.47 h·ng·mL-1), CC-MEs (2808.51 h·ng·mL-1) and tincture (1500.16 h·ng·mL-1). Also, AUCplasma (0–12 h) for MEs (39.35±13.90 h·ng·mL-1) was significantly lower than HC-MEs (66.32 h·ng·mL-1), CC-MEs (59.70 h·ng·mL-1) and tincture (73.02 h·ng·mL-1).Conclusion: These combined results suggested that the MEs developed could be a promising and safe alternative for targeted skin delivery of 8-MOP. Keywords: 8-methoxypsoralen, microemulsion, chitosan-coated microemulsion, ex vivo permeation, microdialysis, pharmacokinetics