pH 敏感的巯基化阳离子水凝胶用于口服胰岛素传递。

pH sensitive thiolated cationic hydrogel for oral insulin delivery.

出版信息

J Biomed Nanotechnol. 2014 Apr;10(4):642-50. doi: 10.1166/jbn.2014.1740.

DOI:10.1166/jbn.2014.1740

Abstract

The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%.

摘要

本工作旨在研究 pH 敏感的巯基化聚二甲基氨基乙基甲基丙烯酸酯用于胰岛素的口服递送。通过碳二亚胺化学将聚甲基丙烯酸与巯基化聚二甲基氨基乙基甲基丙烯酸（PDCys）交联，合成 pH 敏感的巯基化聚二甲基氨基乙基甲基丙烯酸（PDCPA）。在进行体内实验之前，进行了各种物理化学和生物学特性评估，以评估 PDCPA 的疗效。通过 IR 和 NMR 光谱证实了修饰。粒径为 284nm，zeta 电位为 37.3+/-1.58mV。纹理分析器测量表明 PDCPA 比母体聚合物具有更强的粘膜粘附性。跨上皮电测量表明，在用 PDCPA 颗粒孵育时，减少超过 50%。渗透研究表明 PDCPA 比母体聚合物更具渗透性。在雄性糖尿病大鼠的体内评价中，负载胰岛素的 PDCPA 使血糖降低了 19%。