Zhang Haibin, Gu Zhiyang, Li Wenya, Guo Lili, Wang Litong, Guo Lan, Ma Saibo, Han Baoqin, Chang Jing
College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China.
College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China; Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266235, PR China.
Int J Biol Macromol. 2022 Dec 31;223(Pt A):433-445. doi: 10.1016/j.ijbiomac.2022.10.274. Epub 2022 Nov 5.
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.
口服给药因其患者顺应性高且侵入性小而被认为是最优选的治疗方式。然而,蛋白质药物的口服给药一直是个难题,由于蛋白质在胃肠道中渗透不稳定且效率低下,限制了其应用。在本研究中,通过使用O-羧甲基壳聚糖(OCMC)和海藻酸钠(SA)制备了一种新型的OCMC/SA纳米水凝胶来解决该问题。OCMC/SA具有典型的纳米结构,这有助于增加比表面积并提高药物的生物利用度。OCMC/SA具有高载药能力,并通过响应微环境的不同pH值实现被动药物靶向功能。它在强酸环境下对药物有一定的保护作用,而在肠道环境中其结构会松散并有效释放药物。OCMC/SA可以释药超过12小时,且释放出的胰岛素能保持高活性。OCMC/SA纳米水凝胶在1型糖尿病大鼠中显示出有前景的结果,其药理生物利用度为6.57%。总之,本研究构建了一种新型的OCMC/SA纳米水凝胶,它具有许多令人兴奋的特性,并为口服给药提供了一种新策略。