pH-sensitive O-carboxymethyl chitosan/sodium alginate nanohydrogel for enhanced oral delivery of insulin
Haibin Zhang, Zhiyang Gu, Wenya Li, Lili Guo, Litong Wang, Lan Guo, Saibo Ma, Baoqin Han, Jing Chang
Abstract
Oral drug delivery is considered the most preferred mode of treatment because of its high patient compliance and minimal invasiveness. However, the oral delivery of protein drug has been a difficult problem which restricts its application due to the unstable and inefficient penetration of protein in the gastrointestinal tract. In this study, a novel OCMC/SA nanohydrogel was prepared by using of O-carboxymethyl chitosan (OCMC) and sodium alginate (SA) to solve the problem. The OCMC/SA had a typical nanostructure, which was helpful to increase the specific surface area and enhanced the bioavailability of the drugs. OCMC/SA had a high drug loading capacity and realized passive drug targeting function by responding to the different pH value of the microenvironment. It could have a certain protective effect on drugs in strong acid circumstances, while its structure got loosed and effectively released drugs in intestinal circumstances. OCMC/SA could release the drug for >12 h, and the released insulin could maintain high activity. OCMC/SA nanohydrogel showed promising results in type 1 diabetic rats, and its pharmacological bioavailability was 6.57 %. In conclusion, this study constructed a novel OCMC/SA nanohydrogel, which had a lot of exciting characteristics and provided a new strategy for oral drug delivery.