Pharmacodynamics And Safety Evaluation Of Clobetasol Propionate Liposome

OBJECTIVE: Clobetasol propionate(CP) liposome was prepared successfully with the method of revolution thin film dispersion in the preliminary experiment.This experiment was aimed at further study of the efficiency and safety of CP liposome on guinea pig models of eczema.METHODS: 1. Pharmacodynamic study: The right ears of 40 guinea pigs were repeatedly challenged with a small dose of dinitrochlorobenzene(DNCB) to establish the models of chronic eczema. The prepared 40 guinea pigs of chronic eczema model were divided into 4 groups,each group included 10 guinea pigs. They were given CP liposome, CP cream, blank liposome and saline respectively twice a day for 14 days. After the drug withdrawl for 1 day, we mesured the thickness of the right and left ears of each animal using micrometer diameter with single-blind method, and their thickness differences were evaluated. Then all the guinea pigs were killed with decapitation. About 0.5cm×0.5cm area tissues in the right ears were harvested and fixed with 10% formalin, then the hematoxylin and eosin (HE) histologic examination was performed. With optical microscope, the average amount of inflammatory cells which infiltrated into the dermis were counted under 10 high power field(HPF). The results of the inflammatory cells and the differences of swelling degree between the right and left ears were used to evaluate the curative effect of CP liposome. 2. Safety evaluation: The hair covering the surface of the right abdominal (about 6cm×6cm) of 20 guinea pigs was removed using 8% sodium sulfide, then CP liposome and CP cream were administered respectively once a day for 8 weeks. After that, all guinea pigs were killed. About 0.5cm×0.5cm area tissues were harvested and fixed with 10% formalin, also the HE histologic examination was performed. The epidermal cell layers were calculated and compared to evaluate the safety of CP liposome.RESULT: 1. Pharmacodynamics study: The inflammatory cells which infiltrated in dermis in the CP liposome group (9.46±0.48/HPF) was notably less than that in the CP cream group(18.52±1.94/HPF) (P<0.05).The thickness differences between the right and left ears in the CP liposome group and the CP cream group were 0.15±0.04mm and 0.14±0.05mm respectively, their results had no statistically difference (P>0.05). 2.Safety evaluation: The epidermal cell layers in CP liposome group and the CP cream group were 4.93±0.75/HPF and 2.00±0.44/HPF respectively, it had significant statistically difference( P<0.05).CONCLUSION: 1.Pharmacodynamic study: CP liposome can effectively reduce both the number of inflammatory cells in the dermis and the ear swelling degree. Compared with CP cream, the curative effect of CP liposome on guinea pig models of chronic eczema is better. 2.Safety evaluation: The application of CP cream for eight weeks caused obvious reduction of the epidermal cells layers, while the result of CP liposome was nearly normal. That indicates CP liposome has higher safety than CP cream in the long-term administration.