可注射CS/PLLA-SA复合水凝胶的制备及载药性

Preparation and drug loading properties of an injectable CS/PLLA-SA composite hydrogel

采用先核后臂法以及丁二酸酐(SA)羧基化修饰合成了末端为羧基的四臂星型聚乳酸(PLLA-SA),将其加入丙酮中得到PLLA-SA纳米分散液。壳聚糖(CS)与分散液通过静电作用自组装形成可注射CS/PLLA-SA复合水凝胶,采用Zeta电位及激光粒度仪、FTIR和SEM等对PLLA-SA、分散液及水凝胶的组成、结构和性能进行表征与测定。结果表明,PLLA-SA的Zeta电位值为–21.89 mV,其分散液的平均粒径为216 nm。在温度为15℃,PLLA-SA质量浓度为5 g/L,布洛芬(IBU)与PLLA-SA质量比为1∶2,650 r/min搅拌1 h,550 r/min搅拌4h的条件下,制备出载IBU的PLLA-SA分散液。将该分散液与质量浓度为10g/L的壳聚糖盐酸盐(CS-HCl)水溶液按体积比为7∶3混合,快速自组装形成载药CS/PLLA-SA复合水凝胶,包封率和载药量分别达到85.38%和28.46%。体外药物释放结果表明,可注射载药水凝胶对IBU具有明显的缓释作用,30h内药物的累积释放率可达到95.81%。

A four-armed star-shaped polylactic acid(PLLA-SA)copolymer with carboxyl carboxyl terminus was synthesized by core-first technique and carboxylation of succinic anhydride(SA),and was dispersed into acetone to obtain PLLA-SA nano-dispersion solution.Then,an injectable CS/PLLA-SA composite hydrogel was obtained by electrostatic action between chitosan(CS)and the dispersion.The composition,structure and properties of PLLA-SA,PLLA-SA nano-dispersion and CS/PLLA-SA hydrogel were characterized by laser particle size and Zeta potential analyzer,FTIR and SEM.The Zeta potential value of PLLA-SA was–21.89 m V,the average particle size of PLLA-SA nano-dispersion solution was 216 nm.Ibuprofen(IBU)-PLLA-SA nano-dispersion solution was prepared under the conditions of temperature of 15℃,PLLA-SA mass concentration of 5 g/L,m(IBU)∶m(PLLA-SA)=1∶2,stirring speed of 650 r/min for 1 h,then 550 r/min for 4 h.The IBU-PLLA-SA nano-dispersion was mixed chitosan hydrochloride(CS-HCl)with a mass concentration of 10 g/L at a volume ratio of 7∶3,which was rapid self-assembly to form a drug-loaded CS/PLLA-SA composite hydrogel.The loading efficiency and loading content of the composite hydrogel reached 85.38%and 28.46%,respectively.In vitro drug release results indicated that the injectable CS/PLLA-SA composite hydrogel exhibited an obvious sustained-release capability for IBU,and the cumulative release rate of IBU within 30 h could reach 95.81%.