口服胰岛素载体的高分子生物材料

doi:10.3969/j.issn.2095-4344.2013.38.021

中国组织工程研究

• 生物材料综述 biomaterial review • 上一篇下一篇

口服胰岛素载体的高分子生物材料

李玉萍，孙利珍，熊向源，李资玲，龚妍春，韩笑

江西科技师范大学生命科学学院，江西省南昌市 330013

收稿日期:2013-03-11 修回日期:2013-03-20 出版日期:2013-09-17 发布日期:2013-09-17
作者简介:李玉萍☆，女，1964年生，重庆市人，汉族，2004年日本九州大学毕业，博士，教授，主要从事生物功能材料方面研究与开发。liyp20012000@yahoo.com.cn
基金资助:
国家自然科学基金项目(81060264)*；江西省青年科学家(井冈之星)培养对象计划(2008DQ01600)*；国家自然科学基金项目(21264009)*；人事部留学人员科技活动项目([2010]412)*；江西省教育厅科学技术研究项目 (GJJ10594)*

Biodegradable polymeric biomaterials as oral insulin carriers

Li Yu-ping, Sun Li-zhen, Xiong Xiang-yuan, Li Zi-ling, Gong Yan-chun, Han Xiao

School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, Jiangxi Province, China

Received:2013-03-11 Revised:2013-03-20 Online:2013-09-17 Published:2013-09-17
About author:Li Yu-ping☆, Doctor, Professor, School of Life Science, Jiangxi Science & Technology Normal University, Nanchang 330013, Jiangxi Province, China liyp20012000@yahoo.com.cn
Supported by:
the National Natural Science Foundation of China, No. 81060264*; the Training Plan for Young Scientists in Jiangxi Province, No. 2008DQ01600*; the National Natural Science Foundation of China, No. 21264009*; the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Ministry of Personnel, No. [2010]412*; the Scientific and Technological Research Program of Jiangxi Provincial Education Committee, No. GJJ10594*

摘要/Abstract

摘要：

背景：利用具有生物相容性和生物可降解性的高分子材料作为载体，通过化学结合或物理包裹胰岛素，可提高胰岛素在体内的稳定性和生物利用度。
目的：从类型、制备方法、特征、药理作用等方面综述国内外口服胰岛素载体的高分子材料的研究进展。
方法：由作者应用计算机检索中国知网数据库、PubMed数据库和Elsevier 数据库2002年1月至2013年2月，与高分子生物材料和口服胰岛素载体相关的文章，中文关键词为“高分子生物材料、口服胰岛素、载体”，英文关键词为“polymeric biomaterials，oral insulin，carrier”。
结果与结论：目前，主要用于口服胰岛素系统控缓释的高分子生物材料可分为天然高分子生物材料和合成高分子生物材料两大类。用于口服胰岛素载体研究的天然高分子材料，以壳聚糖、藻酸盐多见。合成高分子生物材料中聚酯类、聚丙烯酸酯类及其共聚物，因具有良好的生物相容性、生物降解性和生理性能，被用作口服胰岛素制剂的载体材料的研究报道较多。国内外有关口服胰岛素制剂的研究报道虽多，也有一些商品型口服胰岛素进入临床试验阶段，但至今尚未见到实际应用的临床报告。其主要原因是作为载体的高分子材料、胰岛素的生物利用度低、制剂的质量标准及稳定性问题尚未解决。因此，未来的研究将主要集中在：载体材料的选择或者对现有高分子聚合物进行物理和化学的修饰，研发出新型的聚合物基材料作为载体，以避免胃肠道对胰岛素的破坏和改善胰岛素在体内的吸收，获得理想的释药速度和良好缓控释效果。

关键词: 生物材料, 生物材料综述, 高分子生物材料, 口服胰岛素, 载体, 壳聚糖, 藻酸盐, 聚酯类, 聚丙烯酸酯类, 国家自然科学基金

Abstract:

BACKGROUND: The carriers made from biodegradable and biocompatible polymeric materials represent an exciting approach to increase the bioavailability and stability of orally administered insulin by the chemical reaction or physical encapsulation of insulin.
OBJECTIVE: To mainly review the research progress of the material types, preparation methods, physicochemical characteristics, in vitro release kinetics, and bioavailability of polymeric materials adopted as oral insulin carriers.
METHODS: The first author searched PubMed, Elsevier and CNKI databases for articles (2002-01/2013-02) concerning the polymeric materials and oral insulin carriers with the key words of “polymeric biomaterials, oral insulin, carrier” in English and in Chinese.
RESULTS AND CONCLUSION: Currently, there are mainly two kinds of polymeric biomaterials used for oral insulin delivery systems, that is, natural polymeric biomaterials (such as chitosan and alginates) and synthetic polymeric biomaterials. The most commonly used synthetic polymeric materials for the preparation of these vehicles are polyesters, polyacrylates and their copolymers, which are well known for their good biodegradability, biocompatibility, and physiological properties. Although researchers have tried to develop promptly oral insulin formulation using various technologies, the reports about clinical application or commercial success have not been seen because of several questions such as polymer material as a carrier, the lower bioavailability of insulin, the quality standards and stability of the formulation. Hence, future studies will focus on the development of a new type of polymer-based material as carriers by choosing the new materials or modifying physical and chemical characteristics of existing polymers, to avoid gastrointestinal destruction of the insulin and increase bioavailability of insulin in the body, so as to obtain the good controlled release rate and effect.

Key words: biocompatible materials, review, chitosan, insulin, polypropylenes

中图分类号:

R318

李玉萍，孙利珍，熊向源，李资玲，龚妍春，韩笑. 口服胰岛素载体的高分子生物材料[J]. 中国组织工程研究, doi: 10.3969/j.issn.2095-4344.2013.38.021.

Li Yu-ping, Sun Li-zhen, Xiong Xiang-yuan, Li Zi-ling, Gong Yan-chun, Han Xiao. Biodegradable polymeric biomaterials as oral insulin carriers[J]. Chinese Journal of Tissue Engineering Research, doi: 10.3969/j.issn.2095-4344.2013.38.021.

图/表（结果） 1

参考文献

[1] Ramesan RM,Sharma CP.Challenges and advances in nanoparticle-based oral insulin delivery. Expert Rev Med Devices.2009; 6(6): 665-676.
[2] Wawrezinieck A,Péan JM,Wüthrich P,et al.Oral bioavailability and drug/carrier particulate systems. Med Sci (Paris).2008; 24(6-7): 659-664.
[3] Di Marco M,Shamsuddin S,Razak KA,et al.Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation, and encapsulation.Int J Nanomed. 2010;5: 37-49.
[4] Chaturvedi K,Ganguly K,Nadagouda MN,et al. Polymeric hydrogels for oral insulin delivery.J Control Release.2013; 165(2): 129-138.
[5] Sonia TA,Sharma CP.An overview of natural polymers for oral insulin delivery. Drug Discov Today.2012;17(13-14):784-792.
[6] Aksungur P,Sungur A,Unal S,et al.Chitosan delivery systems for the treatment of oral mucositis: in vitro and in vivo studies. J Control Release.2004; 98(2): 269-279.
[7] Sonaje K,Chuang EY,Lin KJ,et al.Opening of epithelial tight junctions and enhancement of paracellular permeation by chitosan: microscopic, ultrastructural, and computed- tomographic observations.Mol Pharm.2012; 9(5): 1271-1279.
[8] Sonaje K,Lin KJ,Tseng MT,et al.Effects of chitosan-nanoparticle-mediated tight junction opening on the oral absorption of endotoxins. Biomaterials. 2011;32(33): 8712-8721.
[9] Wang LY,Gu YH,Su ZG,et al.Preparation and improvement of release behavior of chitosan microspheres containing insulin. Int J Pharm.2006;311(1-2): 187-195.
[10] 邵丽,邓阳全,吴旭,等.载药壳聚糖缓释微球的制备及其释放研究[J].功能材料, 2009,40(6): 959-961,965.
[11] 董宝军,王常勇,郭希民,等.口服壳聚糖胰岛素纳米粒的制备及其降血糖作用研究[J].解放军医学杂志,2005,30(3): 208-210.
[12] 张立强,陶安进,石凯,等.肠溶包衣胰岛素壳聚糖复合物纳米粒的制备及体内外性质[J].沈阳药科大学学报,2006,23(2): 65-68.
[13] Pan Y,Li YJ,Zhao HY,et al.Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo.Int J Pharm.2002;249 (1-2): 139-147.
[14] Makhlofa A,Tozuka Y,Takeuchia H.Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery. Eur J Pharm Sci.2011;42: 445-451.
[15] Chuang EY,Lin KJ,Su FY,et al.Calcium depletion-mediated protease inhibition and apical-junctional-complex disassembly via an EGTA-conjugated carrier for oral insulin delivery.J Control Release. 2012; 27: in press.
[16] Elsayed A,Al-Remawi M,Qinna N,et al.Chitosan-sodium lauryl sulfate nanoparticles as a carrier system for the in vivo delivery of oral insulin. AAPS Pharm Sci Tech.2011;12(3): 958-964.
[17] 吴正红,平其能,陈燕,等.N-三甲基壳聚糖盐酸盐包覆胰岛素脂质体的处方与工艺优化[J].中国药科大学学报,2003,34(4): 322-326.
[18] Wu ZH,Ping QN,Li JY,et al.Effect of Liposome Double-Coated with Chitosan and Chitosan-EDTA Conjugates on Oral Absorption of Insulin. J Chine Pharm Sci.2006;15(3): 139-146.
[19] 王春,杨连生,扶雄. 水溶性壳聚糖纳米粒子的制备及其BSA载药性能[J].化工进展,2006,25(12): 1431-1435.
[20] Reis CP,Ribeiro AJ,Neufeld RJ,et al.Alginate microparticles as novel carrier for oral insulin delivery. Biotechnol Bioeng. 2007; 96(5): 977-989.
[21] 杨利芳,薛伟明,高茜,等. 载胰岛素壳聚糖微球口服降血糖作用的研究[J].化学工程,2008,36(1): 71-74.
[22] Zhang YL,Wei W,Lv PP,et al.Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin. Eur J Pharm and Biopharm. 2011; 77(1): 11-19.
[23] Li XY,Qi JP,Xie YC,et al.Nanoemulsions coated with alginate/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats.Int J Nanomedicine.2013;8: 23-32.
[24] Woitiski CB,Neufeld RJ,Ribeiro AJ,et al.Colloidal carrier integrating biomaterials for oral insulin delivery: Influence of component formulation on physicochemical and biological parameters. Acta Biomater.2009;5(7): 2475-2484.
[25] Woitiski CB,Sarmento B,Carvalho RA,et al.Facilitated nanoscale delivery of insulin across intestinal membrane models.Int J Pharm.2011;412(1-2): 123-131.
[26] Jederstrom G,Anderss on A,Grasjo J,et al.Formulating insulin for oral adminst ration: preparation of hyaluroman-insulin complex.Pharm Res. 2004;99: 2040-2047.
[27] Han L,Zhao Y,Yin L,et al.Insulin-loaded pH-sensitive hyaluronic acid nanoparticles enhance transcellular delivery. AAPS Pharm Sci Tech. 2012; 13(3): 836-845.
[28] 黄建艳,包磊,毛萱,等.琼脂糖-透明质酸共聚物作为胰岛素载体[J].材料科学与工程学报,2009,27(1): 43-46.
[29] 郑健,岳秀丽,王洋,等.一种基于硫酸葡聚糖铁复合物的胰岛素缓释微胶囊及其降血糖活性[J].中国组织工程研究与临床康复, 2008,12(36): 7045-7048.
[30] 陈军,易以木.口服胰岛素聚乳酸纳米粒的研制[J].中国现代应用药学杂志,2003, 20(4): 263-265
[31] 钱良山,王小鹏,陈天宁.聚乳酸-羟基乙酸药物控释微型装置的制备[J].中国医药工业杂志,2006,37(5): 322.
[32] 潘妍,李英剑,高鹏,等.壳聚糖包衣对胰岛素聚酯纳米粒胃肠道吸收的促进作用[J].药学学报,2003,38(6): 467-470 .
[33] 张雪飞,胡俊丽,陈学思，等.载有胰岛素的可生物降解微球的制备与表征[J].高等学校化学学报,2005,26(3): 554-557.
[34] 陶安进,张立强,石凯,等.胰岛素肠溶PLGA纳米粒的制备及体内外性质的评价[J].沈阳药科大学学报,2007,24(1):9-13.
[35] Hinds KD,Campbell KM,Holland KM,et al.PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis.J Control Release.2005; 104(3): 447-460.
[36] Xiong XY,Li YP,Li ZL,et al.Vesicles from Pluronic/poly(lactic acid) block copolymers as new carriers for oral insulin delivery. J Controlled Release. 2007;120: 11-17.
[37] 庞伟,杨红,陆彬.胰岛素聚β羟基丁酸酯微球体外性质的研究[J].中国药师, 2008,11(10): 1138-1140.
[38] 李松,张华,王学清,等.一种胰岛素口服纳米骨架给药系统的体内外初步研究[J]. 中国药学杂志,2011,46(19): 1496-1500.
[39] Damgé C,Socha M,Ubrich N,et al.Poly(epsilon-caprolactone) /eudragit nanoparticles for oral delivery of aspart-insulin in the treatment of diabetes.J Pharm Sci.2010;99(2): 879-889.
[40] Mesiha MS,Sidhom MB,Fasipe B.Oral and subcutaneous absorption of insulin poly(isobutylcyanoacrylate) nanoparticles. Int J Pharm.2005; 288: 289-293.
[41] Hou ZQ,Zhang ZX,Xu ZH,et al.The stability of insulin-loaded polybutylcyanoacrylate nanoparticles in an oily medium and the hypoglycemic effect in diabetic rats. Acta Pharmaceutica Sinica.2005; 40(1): 57-64.
[42] Kumar A,Lahiri SS,Singh H.Development of PEGDMA: MAA based hydrogel microparticles for oral insulin delivery.Int J Pharm.2006;323(1-2): 117-124.
[43] Yin L,Ding J,Zhang J,et al.Polymer integrity related absorption mechanism of superporous hydrogel containing interpenetrating polymer networks for oral delivery of insulin. Biomaterials.2010;31(12): 3347-3356.

口服胰岛素载体的高分子生物材料

Biodegradable polymeric biomaterials as oral insulin carriers

PDF

可视化

被引次数

摘要/Abstract

引用本文

使用本文

图/表（结果） 1

参考文献

相关文章 15

引言

材料方法

讨论

文章快阅

延伸阅读

编辑推荐

Metrics

本文评价

[1]	李黎, 马力. 磁性壳聚糖微球固定化乳糖酶及其酶学性质[J]. 中国组织工程研究, 2021, 25(4): 576-581.
[2]	张振坤, 李喆, 李亚, 王莹莹, 王亚苹, 周馨魁, 马珊珊, 关方霞. 海藻酸盐基水凝胶/敷料在创面愈合中的应用：持续、动态与顺序释放[J]. 中国组织工程研究, 2021, 25(4): 638-643.
[3]	刘鋆, 杨龙, 王伟宇, 周玉虎, 吴颖, 卢涛, 舒莉萍, 马敏先, 叶川. 聚3-羟基丁酸酯4-羟基丁酸酯/聚乙二醇/氧化石墨烯组织工程支架的制备和性能评价[J]. 中国组织工程研究, 2021, 25(22): 3466-3472.
[4]	李鑫平, 崔秋菊, 曾曙光, 冉高英, 张兆强, 刘显文, 方炜, 徐帅妹. β-磷酸三钙/壳聚糖水凝胶改性对牙髓干细胞生长与矿化的影响[J]. 中国组织工程研究, 2021, 25(22): 3493-3499.
[5]	刘珂珂, 段昕, 马向瑞, 张云涛. 以电纺丝膜为载体观察桂皮醛对高糖环境下成骨细胞的影响[J]. 中国组织工程研究, 2021, 25(22): 3500-3504.
[6]	周安琪, 唐渝菲, 吴秉峰, 向琳. 骨膜组织工程设计：共性与个性的结合[J]. 中国组织工程研究, 2021, 25(22): 3551-3557.
[7]	郎丽敏, 何生, 姜增誉, 胡奕奕, 张智星, 梁敏茜. 导电复合材料在心肌梗死组织工程治疗领域的应用进展[J]. 中国组织工程研究, 2021, 25(22): 3584-3590.
[8]	陈思宇, 李燕楠, 颉丽英, 刘司麒, 范玉蓉, 房昌星, 张鑫, 权家宇, 左琳. 负载碱性成纤维细胞生长因子温敏性壳聚糖-胶原复合水凝胶可减缓小鼠心肌梗死后心室的重构[J]. 中国组织工程研究, 2021, 25(16): 2472-2478.
[9]	刘冯, 张瑜, 王燕丽, 骆威, 韩超珊, 李杨欣. 温敏型壳聚糖水凝胶包封外泌体在缺血性疾病中的应用[J]. 中国组织工程研究, 2021, 25(16): 2479-2487.
[10]	李洁, 许楗桢, 胡萍, 雷琪琪, 张文柠, 敖宁建. 用于慢性伤口羧甲基壳聚糖/氧化葡甘聚糖/三七总皂苷复合海绵的制备及性能评价[J]. 中国组织工程研究, 2021, 25(16): 2528-2534.
[11]	干洲杰, 裴锡波. 酶响应性纳米粒子治疗肿瘤：纳米粒子积累和药物释放的优势[J]. 中国组织工程研究, 2021, 25(16): 2562-2568.
[12]	解健, 苏俭生. 静电纺丝取向纳米纤维作为组织工程生物支架的优势与特征[J]. 中国组织工程研究, 2021, 25(16): 2575-2581.
[13]	纪琦, 喻正文, 张剑. 3D打印金属基生物材料工艺和临床应用的问题与趋势[J]. 中国组织工程研究, 2021, 25(16): 2597-2604.
[14]	宋涯含, 吴云霞, 范道洋. 基于VOSviewer生物医学领域3D打印的知识图谱分析[J]. 中国组织工程研究, 2021, 25(15): 2385-2393.
[15]	钱楠楠, 张潜, 杨睿, 敖俊, 章涛. 间充质干细胞治疗脊髓损伤：细胞治疗及联合新药和生物材料[J]. 中国组织工程研究, 2021, 25(13): 2114-2120.