In Vivo Microdialysis for Dynamic Monitoring of the Effectiveness of Nano-liposomes as Vehicles for Topical Psoralen Application

抄録

In this study, the skin permeation of liposomes containing psoralen was investigated by in vivo skin microdialysis. Psoralen-loaded nano-sized liposomes were prepared with a mean size of 117.5 nm and a polydispersity index of 0.21, indicating the uniform dispersion of phosphatidylcholine vesicles in the liposomal solution. Based on in vivo microdialysis experiments, the drug concentration in local deep skin of rat increased rapidly and reached a peak concentration (C_max) of 319.35±23.72 µg/mL at 180 min, and decreased slowly thereafter. The local area under the concentration–time curve (AUC)_0–t was 3.81-fold higher than the compared aqueous suspension. The in vivo systemic pharmacokinetics were in agreement with the microdialysis results, in view of the C_max and AUC_0–t from liposomal group were both significantly higher (p<0.05) than the compared group. Liposome-associated transdermal psoralen delivery was significantly more effective than delivery via an aqueous suspension. The enhanced skin permeability may be associated with improved skin hydration, lipid exchange and fusion with the stratum corneum (SC), and changes in SC structure, promoting drug permeation into deep skin. After 10 h of treatment with the perfusate, the microstructure of the microdialysis probe exhibited no obvious differences with control probes. The skin surface and the tissue around the probe showed no swelling or inflammation. These findings indicated that liposomes effectively enhanced the skin deposition of psoralen and showed good biocompatibility with skin tissues; additionally, ethanol at a low concentration in ringer’s solution is an alternative perfusate for in vivo skin microdialysis studies.