基于纤维素模板的聚合物空心微球作为药物载体的性能研究及分析

Properties of Cellulose-based Polymeric Hollow Microspheres as Drug Carriers

以羟丙基纤维素为模板材料,分别采用不同的聚合方法制备了2种不同形态和结构的聚合物空心微球——聚N-异丙基丙烯酰胺-co-聚丙烯酸(PNIPAm-co-PAA)微凝胶和聚N-异丙基丙烯酰胺-聚丙烯酸(PNIPAm-PAA)水凝胶微囊。以盐酸阿霉素(Dox)作为模型药物,考察了聚合物空心微球作为药物载体的载药能力和体外释放性能。研究表明,PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊和Dox分子能够通过正负电荷的相互吸引实现有效结合;载药微球具有良好的缓释性能,并对Dox的释放表现出明显的p H值敏感性和温度敏感性。体外细胞毒性实验表明,载药PNIPAmco-PAA微凝胶、PNIPAm-PAA水凝胶微囊具有很高的抗肿瘤活性,细胞相对存活率均可达20%左右。PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊在作为水溶性药物或蛋白类药物载体方面,具有潜在的应用价值,同时有望应用于木材胶黏剂防腐等。

Hydroxypropylcellulose （HPC）, a natural polymer, was chosen as a biocompatible and biodegradable template to prepare two kinds of polymeric hollow microspheres, i. e., poly （ N-isopropylacrylamide ） -co-poly （ acrylic acid ） （ PNIPAm-co- PAA） microgels and poly （N-isopropylacrylamide）-poly （acrylic acid） （PNIPAm-PAA） hydrogel capsules by using different polymerization methods. The drug loading capacity and releasing behaviors of PNIPAm-co-PAA microgels and PNIPAm-PAA hydrogel capsules as drug carriers were investigated by using anticancer drug, Doxorubicin hydrochloride （Dox） , as hydrophilic model drug. The results indicated that Dox could be encapsulated in PNIPAm-co-PAA microgels and PNIPAm-PAA hydrogel capsules with high drug loading driven by the electrostatic interaction. The characteristic sustained-releases of Dox from these two kinds of microspheres were observed under physiological pH and temperature. More encouragingly, the release of Dox exhibited a dual-responsivity to temperature and pH. In vitro cytotoxicity assay indicated that Dox-loaded PNIPAm-co-PAA microgels and PNIPAm-PAA hydrogel capsules had high antitumor activity, and implied that they might be a potential drug delivery carrier especially for water-soluble or polypeptide drugs, as well as applying in the wood adhesive preservation, etc.