聚电解质微球多级自组装制备双重药物载体

DUAL DRUG DELIVERY SYSTEM FROM MULTI-STEP SELF-ASSEMBLED POLYELECTROLYTE NANOPARTICLES

将表面带正电荷的壳聚糖(CS)微球和表面带负电荷的聚(L-谷氨酸)-b-聚氧化丙烯-b-聚(L-谷氨酸)(GPG)胶束共混,制备了CS/GPG聚集体水溶液体系.通过改变CS/GPG的共混比例,研究了CS微球和GPG胶束形成稳定CS/GPG聚集体水溶液体系的配比范围,并对其粒径分布和表面电位进行了表征.在此基础上,将CS微球作为亲水性药物阿司匹林(Asp)的载体,GPG胶束作为疏水性药物阿霉素(DOX)的载体,通过多级自组装形成一种新型双重载药体系.研究了该双重药物载体的体外药物释放行为.结果表明,Asp和DOX都具有很好的药物缓释效果,并且2种药物的释药行为都具有明显的pH值响应性.

Self-assembly of chitosan（CS） particles and poly（L-glutamic acid）-b-poly（propylene oxide）-b-poly（L-glutamic acid）（GPG） triblock copolymer micelles was investigated.The CS particles are cationic hydrogels,while the GPG micelles have anionic poly（L-glutamic acid） shells.Therefore,the two kinds of polyelectrolyte particles can electrostatic self-assemble into microscopic CS/GPG conjugates.The CS/GPG ratio range for the CS particles and GPG micelles to electrostatic self-assemble into a sustained CS/GPG conjugates solution was established.The CS/GPG conjugates were prepared by dropping CS particle solution into GPG micelle solution under stirring,with the CS/GPG ratio of 0.25/10,0.5/10,0.75/10,1.0/10,1.25/10,1.5/10,1.75/10 and 2/10.The CS/GPG conjugates are stable in water when the CS/GPG ratio is equal or less than 1.5/10.The particle size distribution of GPG micelles,CS particles,and CS/GPG conjugates were determined by the dynamic light scattering.GPG micelles show a narrow distribution with the average Rh of 59 nm,while the CS particles and CS/GPG conjugates show much broaden distributions with the Rh of 177 nm and 364 nm respectively.Zeta potential tests show that the GPG micelles exhibit surface negative charge of-52 mV and the CS particles exhibit surface positive charge of 22 mV.The surface charge of CS/GPG conjugates are negative and the average absolute value of the surface charge decreases with increasing CS amount.In vitro drug release behaviors of the Aspirin（Asp）-loaded CS particles,Doxorubicin（DOX）-loaded GPG micelles,and the Asp-CS/DOX-GPG conjugates（CS/GPG=1.5/10） were studied as a function of pH value.Both Asp and DOX show pH sensitive release behaviors in all the three drug-loaded systems.Moreover,the release rate of Asp shows a dramatic decrease in the Asp-CS/DOX-GPG system,as compared with the Asp-CS nanoparticles.