壳聚糖/羟基磷灰石复合微球的原位合成及体外释药性能

In-Situ Synthesis of Chitosan/Hydroxyapatite Composite Microspheres and Their In Vitro Drug Release Behavior

采用原位合成法在乳液体系中制备了壳聚糖/羟基磷灰石(HA)复合微球,并探讨了实验条件对复合微球制备的影响。结果表明,当壳聚糖/HA质量比为4/1时,可以获得球形规则,分散性好,平均粒径为9μm的复合微球。此外,NaOH溶液(1mol/L)的加入量应不少于3mL;交联剂(1mL)的最佳加入浓度为8%;向油相中先加入钙盐比先加入磷酸盐时的成球效果好。以盐酸四环素为模型药物,对复合微球的体外载药和释药性能进行了研究。结果显示,HA的引入大大提高了药物的包封率和载药量,而且使得复合微球比纯壳聚糖微球具有更显著的药物缓释效果。

Chitosan/hydroxyapatite（HA）composite microspheres were in-situ synthesized in an emulsion system,and the effects of various experimental parameters on the preparation of the composite microspheres were investigated.The results show that,the composite microspheres prepared at a chitosan/HA mass ratio of4/1possess a regular shape,high dispersity and an average diameter of 9μm.Moreover,the volume of the added NaOH solution（1mol/L）should be not less than 3mL;the optimal concentration of the cross-linker（1mL）is 8%;the calcium salt rather than the phosphate one should be firstly added to the oil phase.Tetracycline hydrochloride was chosen as a model drug to examine in vitro drug loading and release behaviors of the composite microspheres.It is demonstrated that,the addition of HA efficiently increases the drug-loading percentage and drug entrapment efficiency,and also improves the sustained drug delivery behavior of the chitosan microspheres.