海藻酸钠基pH响应性聚合物胶束的制备及释药性能研究

Preparation of pH-responsive Polymeric Micelles based on Sodium Alginate and Its Drug Release Property

中文关键词:  海藻酸钠  聚合物胶束  pH响应性  生物质材料  药物释放

Key Words:sodium alginate  polymeric micelles  pH-responsiveness  biomass material  drug release

中文摘要:

      采用1-（3-二甲氨基丙基）-3-乙基碳二亚胺盐酸盐（EDC）和N-羟基琥珀酰亚胺（NHS）对海藻酸钠进行改性并制备了海藻酸钠基pH响应性聚合物胶束（以下简称聚合物胶束），分析了EDC/NHS改性前后海藻酸钠的红外光谱（FT-IR）、临界胶束浓度（CMC）、粒径和Zeta电位；利用反溶剂重结晶法将疏水药物金雀异黄酮包裹于聚合物胶束中，并对载药聚合物胶束的包封率、载药量和pH响应性进行了研究。结果表明，经EDC/NHS改性后的海藻酸钠可在水中形成聚合物胶束，其CMC为0.041 mg/mL；当聚合物胶束与金雀异黄酮质量比为10∶1时，聚合物胶束的包封率和载药量分别为74.4%和8.6%；体外溶出实验表明，载药聚合物胶束具有良好的pH响应性，其在酸性条件（pH值=2.0）下相对稳定，在中性条件（pH值=7.4）下能释放药物，其有望用作口服型肠吸收药物的载体，以实现药物的缓释和控释。

Abstract:

      In this study sodium alginate （SA） was modified with 1-ethyl-3-（3-dimethylaminopropyl） carbodiimide hydrochloride （EDC） and N-hydroxysuccinimide （NHS）， then the sodium alginate-based pH-responsive polymer micelles were prepared. The Fourier transform infrared spectroscopy （FT-IR）， critical micelle concentration （CMC）， particle size， and Zeta potential were analyzed for SA before and after modified by EDC/NHS. The genistein was then encapsulated in polymeric micelles based on anti-solvent recrystallization method， and the drug loading efficiency， drug loading capacity， and pH responsiveness of the polymer micelles were studied. The results showed that EDC/NHS-modified SA could form polymer micelles in water， and its CMC was 0.041 mg/mL. The loading efficiency and drug loading capacity of polymeric micelles were 74.4% and 8.6%， respectively when the mass ratio of polymeric micelles to genistein was 10∶1. The in vitro release study showed that the polymeric micelles loaded with drug were pH-responsive and relatively stable under acidic conditions （pH value=2.0）， and would release drugs under neutral conditions （pH value =7.4）， enabling it to be used as a carrier for oral drugs absorbing by intestinal tract， so as to achieve controlled release and sustained release of drugs.