克霉唑醇质体和脂质体的体外经皮渗透性及抗菌性的对比研究

Study on in Vitro Percutaneous Permeabilities and Antibacterial Activities of Clotrimazole-Encapsulated Ethosomes and Liposomes

目的比较醇质体和脂质体作为克霉唑经皮给药载体的体外渗透性及抗菌活性。方法采用注入法制备克霉唑醇质体和脂质体,采用Franz扩散池和鼠皮进行体外渗透实验,HPLC测定药物浓度并计算药物稳态透皮速率、时滞和皮内滞留量;采用二倍稀释法测试抗菌活性。结果测得克霉唑醇质体的经皮渗透速率和皮内滞留量分别是20.4和656.52μg·cm-2,与脂质体相比提高了2.59和1.09倍;醇质体的时滞为0.32h,仅是脂质体的11%。克霉唑醇质体对大肠杆菌、白色念珠菌、金黄色葡萄球菌、铜绿假单胞菌的MIC分别是7.80×10-3,1.95,7.81,31.3μg·L-1,是脂质体MIC的50%,50%,12.5%和50%;MBC的变化趋势与MIC类似。结论克霉唑醇质体的经皮渗透性和抗菌活性都优于其脂质体,醇质体是一种有效的经皮给药载体。

OBJECTIVE To evaluate in vitro penetration characteristics and antibacterial activities of clotrimazole loaded ethosomes as a transdermal delivery in comparison with classic liposomes. METHODS Clotrimazole loaded ethosomes and liposomes were prepared by injection method. The penetration experiments of clotrimazole ethosomes through rat skin were performed by Franz＇s cell. The concentration of clotrimazole was determined by HPLC. The steady flux, lag time and the skin deposition of the drug were calculated. The in vitro antibacterial activities of clotrimazole ethosomes were examined by two fold dilutions against E. coli, C. albicans, S. aureus and P. aeruginosa. RESULTS The steady state transdermal flux of 20.4μg·cm^-2·h^-1 and the skin drug deposition of 656.52 μg·cm^-2 for clotrimazole loaded ethosome were increased by 2.59 and 1.09 times of those of liposome respectively at the end of the 24 h experiment. And the lag time of ethosome was 0.32 h and was only one of minth of that of liposome. The minimal inhibitory concentrations （MIC） of clotrimazole ethosomes against the bacteria mentioned above were 7.80× 10^-3, 1.95, 7.81, 31.3 μg·L^-1 and decreased by 50%, 50%, 12.5% and 50% in contrast to those of liposome, respectively. The change of minimal bactericidal concentration （MBC） was similar to MIC. CONCLUSION The ethosome was the efficient carrier for transdermal delivery of clotrimazole. It had the great transdermal flux and the anti-bacterial activity compared with liposome in vitro.