以聚醚聚酯丙烯酸酯为交联剂的pH响应性水凝胶纳米微球的制备及药物释放研究

Preparation of pH Responsive Hydrogel Nanospheres Using Polyether Polyester Acrylate Crosslinkers and Their Application in Drug Release

以聚乙二醇(M_(w)1000)为引发剂,引发ε-己内酯和L-丙交酯开环聚合,制备聚(己内酯-co-乳酸)-聚乙二醇共聚物二醇(PCLA),用甲基丙烯酸酐封端得到PCLA预聚物单体(PCLAMA),并用红外光谱、核磁氢谱和凝胶渗透色谱对合成产物的组成和结构进行了表征。以PCLAMA为大分子交联剂、N-乙烯基吡咯烷酮和丙烯酸为共聚单体,利用紫外引发聚合制备水凝胶纳米微球(PCLAMA-AP),并对其溶胀、降解、药物释放、细胞毒性等性能进行了分析。结果表明,PCLAMA-AP具有pH响应性,其溶胀率随着pH的增大而变大,其中最佳配比下的纳米微球包载茶多酚的载药量超过57%,132 h的累计释放率达到30%,PCLAMA-AP与人脂肪干细胞共培养48 h后,细胞存活率高于94%,并且纳米微球能成功进入细胞。因此该水凝胶纳米微球具有作为药物载体的潜力,有可能极大地提高茶多酚的生物利用效率。

Poly(ε-caprolactone-co-lactic acid)-PEG copolymer diols(PCLA)were prepared by ring opening polymerization ofε-caprolactone and L-lactide initiated by polyethylene glycol(M_(w) 1000).PCLA prepolymer monomers(PCLAMA)were prepared by end capping with methacrylic anhydride.The composition and structure of the synthesized products were characterized by FTIR,1H-NMR and gel permeation chromatography.Hydrogel nanospheres(PCLAMA-AP)were prepared by UV initiated polymerization,using PCLAMA as a macromolecular cross-linker and N-vinylpyrrolidone and acrylic acid as monomers.Swelling,degradation,drug release and cytotoxicity of the hydrogel nanospheres were analyzed,and results show that the hydrogel nanospheres are pH-responsive and the swelling ratio of the hydrogel increases with pH increasing.The drug loading of tea polyphenol in the hydrogel nanospheres with the best monomer ratio is more than 57%,with cumulative drug release over 132 h reaching almost 30%.The hydrogel nanospheres are non-cytotoxic as evidenced by a cell viability of over 94%after co-culture with human adipose derived stem cells for 48 h,and are also observed to successfully enter the cells.The hydrogel nanospheres thus have potential to be used as drug carriers,which may greatly improve the bioavailability of tea polyphenols.