载穿心莲内酯核-壳型Ca-Alg/pNIPAM微球的制备及性能

Preparation and characterization of andrographolide-loaded core-shell Ca-Alg/pNIPAM microspheres

针对穿心莲内酯(AND)口服给药存在药物苦极问题,拟制备一种有效掩蔽药物苦味且能实现药物控释的微球载体。以海藻酸钠(Na-Alg)和N-异丙基丙烯酰胺(NIPAM)为制备材料,采用静电液滴偶联单体聚合工艺制备了核-壳型AND/Ca-Alg/pNIPAM微球。采用扫描电微观测、红外光谱分析、溶胀实验和体外释药实验等表征微球结构与性能。结果表明:与Ca-Alg微球相比,Ca-Alg/pNIPAM微球具有清晰的核-壳结构;微球平衡溶胀率在32—36℃突降14.6%;微球在模拟胃液中2 h内药物累积释放率低于10%,而在模拟肠液中6—8 h即达到释放平衡且释药动力学符合Reter-Peppas模型。核-壳结构使Ca-Alg/pNIPAM微球在高效负载药物的同时掩蔽了药物苦味,并赋予微球温度/pH双重响应特性,实现了药物肠靶向释放。

Aiming at reducing the strong bitterness taste of andrographolide(AND)during its oral administration,a kind of microspheres for bitterness masking and drug controlled release were prepared.Using sodium alginate(Na-Alg)and N-isopropylacrylamide(NIPAM)as primary materials,AND/Ca-Alg/pNIPAM microspheres with core-shell structure were prepared employing the technology of electrostatic droplets generation coupled with monomer polymerization process.The structure and characteristics of microspheres were performed employing scanning electron microscopy,flourier transformation infrared spectroscopy,swelling test and in vitro release experiments.Compared to Ca-Alg microspheres,Ca-Alg/pNIPAM has clear core-shell structure.A sudden decrease numbered 14.6%of equilibrium swelling ratio in the range of 32-36℃.The cumulative release percent of AND from microspheres in simulated gastric juice was less than 10%during 2-hour,whereas a diffusion equilibrium state was almost achieved after 6-8 h in simulated intestinal fluid which fitted Reter-Peppas kinetic equation.With the core-shell structure,the Ca-Alg/pNIPAM microspheres demonstrated effective drug loading capacity and bitterness covering ability,and exhibited intestinal orientated drug delivery performance based on its temperature/pH durable responsiveness.