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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (2/3): 43-53    DOI: 10.13523/j.cb.2209028
新型药物递送系统研发与应用专题     
高分子纳米材料用于口服胰岛素递送体系*
马品品,熊向源**()
江西科技师范大学生命科学学院 南昌 330013
Polymeric Nanomaterials Used in Oral Insulin Delivery Systems
MA Pin-pin,XIONG Xiang-yuan**()
College of Life Sciences, Jiangxi Science and Technology Normal University, Nanchang 330013, China
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摘要：

皮下注射胰岛素是控制血糖水平最有效的方法,在1型和晚期2型糖尿病患者的治疗中起着至关重要的作用。然而频繁的皮下注射给患者带来了极大的痛苦,因此,针对糖尿病的治疗,目前更倾向采用口服疗法。口服胰岛素可以模拟生理胰岛素的分泌,并对肝脏葡萄糖代谢提供更全面的调节,但胃肠道的吸收不良极大地阻碍了胰岛素口服给药的发展。纳米药物递送系统(nanoscale drug delivery systems,NDDS)的快速发展增加了胰岛素口服给药的可能性。高分子纳米材料是NDDS中一类重要的载体材料,已被广泛用于促进胰岛素口服吸收的研究。它具有生物降解性、生物相容性和储存稳定性等优点,并且其分子链长易于改性、修饰和加工成型。高分子纳米材料可以保护包裹的胰岛素不受酸性变性和酶降解的影响,促进细胞对胰岛素的摄取,从而提高胰岛素的生物利用度。讨论了口服胰岛素的主要生理障碍,总结了近几年用于口服胰岛素递送的高分子纳米材料的研究进展。
关键词： 糖尿病;  高分子纳米粒子;  药物递送系统;  口服胰岛素    
Abstract:

Subcutaneous insulin is the most effective way to control blood sugar levels and plays a crucial role in the treatment of patients with type I and advanced type II diabetes. However, frequent subcutaneous injections bring great pain to patients, so for the treatment of diabetes, oral therapy is preferred at present. Oral insulin can mimic physiological insulin secretion and provide more comprehensive regulation of hepatic glucose metabolism, but the development of oral insulin administration is greatly hampered by gastrointestinal malabsorption. The rapid development nanoscale drug delivery systems (NDDS) of has increased the possibility of oral insulin. Polymeric nanomaterials are important carrier materials in NDDS, which have been widely used to promote oral insulin absorption. They have the advantages of biodegradability, biocompatibility and storage stability, and their molecular chain is long and the structure is easy to be changed, modified and processed. The polymeric nanomaterials can protect the encapsulated insulin from the effects of acid denaturation and enzymatic degradation, promote the uptake of insulin by cells, and thus improve the bioavailability of insulin. This review discusses the main physiological obstacles to oral insulin and summarizes the research progress of polymer nanomaterials for oral insulin delivery in recent years.
Key words: Diabetes mellitus    Polymeric nanoparticles    Drug delivery systems    Oral insulin
收稿日期: 2022-09-14 出版日期: 2023-03-31
ZTFLH:  Q819  
基金资助: *江西省自然科学基金重点项目(20212ACB206003)
通讯作者: **熊向源     E-mail: xy.xiong@qq.com
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马品品
熊向源

引用本文:

马品品, 熊向源. 高分子纳米材料用于口服胰岛素递送体系*[J]. 中国生物工程杂志, 2023, 43(2/3): 43-53.

MA Pin-pin, XIONG Xiang-yuan. Polymeric Nanomaterials Used in Oral Insulin Delivery Systems. China Biotechnology, 2023, 43(2/3): 43-53.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2209028    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I2/3/43

图1  包埋胰岛素的纳米囊泡的结构及其降血糖效果
图2  PEG-b-P(Asp-co-AspPBA)/ P(Asp-co-AspGA-co-AspNTA复合胶束负载[32]
图3  Glu-APD在模拟胃肠道环境中保护胰岛素稳定药物释放
图4  壳聚糖-胰岛素电喷雾纳米球(CIN)注射液与胰岛素释放的原理图[39]
图5  肠道淀粉酶导致纳米水凝胶中聚合物网络的降解[9]
类型 纳米材料载体 策略 克服屏障
聚合物囊泡 FA-P85-PLGA[26] 叶酸受体介导的靶向聚合体的内吞作用 胃酸屏障
mPEG-PolyMet[27] 模拟葡萄糖应答性分泌 胃酸屏障
PS@ins/GOx[28] 多水平血糖自我调节功能的葡萄糖和pH双响应型胰岛素给药 胃酸屏障
聚合物胶束 NCs[30] 模拟纳米分子伴侣 胃酸屏障
DSPE-PCB[31] 模拟病毒的两性离子表面、甜菜碱侧链和超低临界胶束浓度 肠道屏障
CM[32] 葡萄糖响应性 胃酸屏障
树枝状聚合物 G2-AC6[34] PAMAM吸收促进剂 肠道屏障
ICPD[35] PPI树枝状大分子的聚乙二醇化 胃酸屏障
Glu-APD[36] 树枝状低聚肽 肠道屏障
纳米球 CIN[39] 壳聚糖-胰岛素电喷雾纳米球 胃酸屏障
PLGA纳米粒[40] 在酸性介质中对胰岛素的释放具有保护作用 胃酸屏障
INS-TMC-PLGA[41] TCM受体介导的靶向聚合体PLGA纳米粒的内吞作用 胃酸屏障、肠道屏障
纳米凝胶 CS/INS/HS[9] pH-淀粉酶响应型水凝胶 胃酸屏障
InF12-Tre2[44] pH敏感型纳米凝胶 胃酸屏障
P(NIPAM-co-Dex-co-
DDOPBA)[45]		 葡萄糖敏感纳米凝胶 胃酸屏障
表1  高分子纳米材料递送胰岛素策略
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