Biosurface Technology Division, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India.
Acta Biomater. 2010 Aug;6(8):3072-80. doi: 10.1016/j.actbio.2010.02.007. Epub 2010 Feb 6.
In the present study thiol functionalized polymethacrylic acid-polyethylene glycol-chitosan (PCP)-based hydrogel microparticles were utilized to develop an oral insulin delivery system. Thiol modification was achieved by grafting cysteine to the activated surface carboxyl groups of PCP hydrogels (Cys-PCP). Swelling and insulin loading/release experiments were conducted on these particles. The ability of these particles to inhibit protease enzymes was evaluated under in vitro experimental conditions. Insulin transport experiments were performed on Caco-2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. Finally, the efficacy of insulin-loaded particles in reducing the blood glucose level in streptozotocin-induced diabetic rats was investigated. Thiolated hydrogel microparticles showed less swelling and had a lower insulin encapsulation efficiency as compared with unmodified PCP particles. PCP and Cys-PCP microparticles were able to inhibit protease enzymes under in vitro conditions. Thiolation was an effective strategy to improve insulin absorption across Caco-2 cell monolayers, however, the effect was reduced in the experiments using excised rat intestinal tissue. Nevertheless, functionalized microparticles were more effective in eliciting a pharmacological response in diabetic animal, as compared with unmodified PCP microparticles. From these studies thiolation of hydrogel microparticles seems to be a promising approach to improve oral delivery of proteins/peptides.
在本研究中，采用巯基功能化的聚甲基丙烯酸-聚乙二醇-壳聚糖（PCP）基水凝胶微球开发了一种口服胰岛素递药系统。通过将半胱氨酸接枝到 PCP 水凝胶的活化表面羧基上（Cys-PCP）来实现巯基修饰。对这些颗粒进行了溶胀和胰岛素负载/释放实验。在体外实验条件下评估了这些颗粒抑制蛋白酶的能力。在 Caco-2 细胞单层和 Ussing 室装置的离体肠组织上进行了胰岛素转运实验。最后，研究了载胰岛素颗粒在降低链脲佐菌素诱导的糖尿病大鼠血糖水平方面的功效。与未修饰的 PCP 颗粒相比，巯基化水凝胶微球的溶胀程度较小，胰岛素包封效率较低。PCP 和 Cys-PCP 微球能够在体外条件下抑制蛋白酶酶。巯基化是提高胰岛素在 Caco-2 细胞单层中吸收的有效策略，然而，在使用离体大鼠肠组织的实验中，这种效果降低了。尽管如此，与未修饰的 PCP 微球相比，功能化微球在诱发糖尿病动物的药理反应方面更有效。从这些研究中可以看出，水凝胶微球的巯基化似乎是改善蛋白质/肽口服递送的一种很有前途的方法。
