N-三甲基壳聚糖对尼美舒利脂质体的影响及其体外透皮考察  

Study on the effect of N-trimethyl chitosan chloride on the nimesulide liposomal gel in vitro

作　　者：何杨虎[1] 何文[1] 李勇[2] 何平平[2] 肖礼海[2] 孙安琪[2] 

机构地区：[1]武汉大学人民医院药学部,湖北武汉430060 [2]武汉大学药学院,湖北武汉430072

出　　处：《中国医院药学杂志》2008年第9期700-705,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的:研究浓度为1.0%,不同季铵化程度的N-三甲基壳聚糖盐酸盐(N-trimethyl chitosan chloride,TMC)对尼美舒利(nimesulide,NIM)脂质体体外主要性质的影响,并进一步考察其凝胶体系体外透皮的效果。方法:以壳聚糖为原料,采用四步合成法合成不同季铵化程度的TMC,以1H-NMR测定其季铵化程度;并采用薄膜分散法制备分别用TMC包覆或混合的NIM脂质体,使用改良的Franz扩散池考察其凝胶体外透皮效果。结果:合成得到不同季铵化程度的TMC,即TMC20(25%),TMC40(38%)和TMC60(59%);用TMC包覆或混合NIM脂质体,均导致其包封率降低;随着TMC季铵化程度的增加,两者的Zeta电位和平均粒径均逐渐减小,但是前者均大于后者;同时两者均具有一定的缓、控释作用,但后者更有效。分别用TMC包覆与混合NIM脂质体的经皮渗透速率之间差异均具有显著性(P<0.01),大小依次为普通脂质体>TMC60包覆脂质体>TMC40包覆脂质体>TMC20包覆脂质体>TMC60混合脂质体>TMC40混合脂质体>TMC20混合脂质体。结论:使用TMC包覆或混合NIM脂质体,可以不同程度地改变NIM脂质体的性质,且作用大小与TMC季铵化程度有关。OBJECTIVE To study the effect of N-trimethyl chitosan chloride （TMC） of 1.0% w/v and its different degrees of quaternization on the nimesulide （NIM） liposomal gels,and their cutaneous penetration in vitro. METHODS TMCs were synthesized from chitosan. The degrees of quaternization of TMCs were determined by ^1H-NMR. The NIM liposomes were prepared by the film dispersion method, followed by the TMCs coating or blending. The Franz-diffusion cells were employed to compare the permeation rate of the NIM liposomal gels in vitro. RESULTS The degree of quaternization of TMC was TMC20, TMC40 and TMC60, respectively. The TMC could decrease the entrapment efficiency of NIM liposomes when they were used. And with the increased of the degree of quaternization of TMC, the mean diameters and the Zeta-potentials of TMC coated or blended NIM liposomes were increased gradually, while the coated ones were always more than the blended ones. Meantime they both showed the sustained release property, and the TMC blended ones were more effective. Significant differences were found on the TMC coated ones when compared to the TMC blended ones（P〈0. 01）,And the order of the steady penetration rate of TMC effected-liposomes was NIM lipsomes〉TMC60 coated-NIM liposomes〉TMC40 coated-NIM liposomes〉TMC20 coated- NIM liposomes〉TMC60 blended-NIM liposomes〉 TMC40 blended-NIM liposomes〉TMC20 blended-NIM liposomes. CONCLUSlON The results suggeste that the TMC could change some properties of NIM liposomes, and the effect is influenced by the degrees of quaternization of TMC.

关 键 词：N-三甲基壳聚糖盐酸盐 包覆 混合 尼美舒利 脂质体凝胶 体外透皮 

分 类 号：R943[医药卫生—药剂学]