Preparation of insulin chitosan nanoparticles loaded pellets for small intestine and colon specific delivery and its oral pharmacodynamics evaluation
Objective To prepare insulin loaded chitosan nanoparticles (Ins-Cs-NPs),small intestine and colon specific delivery Ins-Cs-NPs loaded pellets and evaluate its oral pharmacodynamics effects.Methods Ins-Cs-NPs were prepared by the polyelectrolyte complexation method,then Ins-Cs-NPs was sprayed onto blank pellets core using Polyvinyl Pyrrolidone k30 as coating material to form Ins-Cs-NPs loaded pellets.Small intestine specific delivery was achieved by coating these pellets with Eudragit L30D-55,colon specific delivery was achieved by double-layer coating of chitosan and Eudragit L100.The appearance,particle size,encapsulation efficiency of Ins-Cs-NPs was observed and determined by relative instruments,the coating weight gain (CWG) of different pellets were optimized by dissolution test,the pharmacodynamics effects of all the preparation were evaluated by determing the plasma glucose level after dose.Results The particle size was increased from (163.2±57.4) nm to (210.4±87.4)nm after solidified into pellets,and encapsulation efficiency decreased from (46.6±5.2)% to (42.9±6.8)%.Ins-Cs-NPs could partial protect insulin from degradation by pepsin or pancreatin within 1 hour.Dissolution test showed that 30% CWG of Eudragit L30D-55 could achieve good small intestine specific dedivery,and 40% CWG of chitosan combine with 30% CWG of Eudragit L100 controlled insulin almost unreleased in enzyme free medium but released when incubated with contents of colon in vivo.All the subcutaneous injected groups showed significant hypoglycemic effect,however,all the oral groups neither nanoparticle suspension nor site specific pellets had such effect.Conclusions The particle size,encapsulation efficiency and bioactivity of insulin can be maintained when processed liquid Ins-Cs-NPs suspension into solid pellets by fluid-bed coater.But,the inherent structural defect of Ins-Cs-NPs made it less effective after oral administration wherever the gastric intestinal position they were delivered.
insulin chitosan nanoparticle pellets small intestine and colon specific dellivery
Xiongwei Hu Yi Lu Jianping Qi Wei Wu
School of Pharmacy, Fudan University, Shanghai 201203, China
国内会议
乌鲁木齐
英文
96-98
2013-09-21（万方平台首次上网日期，不代表论文的发表时间）