Challenges and strategies of oral insulin delivery
文献类型：会议论文
| 作者 | Gan Y(甘勇)
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| 出版日期 | 2016-11-18 |
| 关键词 | oral Challenges and strategies of oral insulin delivery |
| 页码 | 2 |
| 英文摘要 | Diabetes mellitus is the most prevalent metabolic disease all over the world now and there are about 415 million diabetic patients till 2015.For the patients who need insulin treatment,subcutaneous injection is the routine administration route which causes pain and trauma resulting in poor patient compliance.Thus,novel insulin formulations are aimed to facilitate the oral delivery,be long-acting and liver-targeting.Among these,oral delivery of insulin has attracted tremendous interest and efforts from both the academic and industrial pharmaceutical scientists in the past decade.There are about ten companies carrying out the clinical trials on oral insulin delivery.For example,Nodlin(Shanghai Biolaxy) and Oshadi Icp are now in Phase I.Capsulin(Diabetology),IN-105(Biocon),NN1953(Novo Nordisk) and ORMD-0801(Oramed) are in Phase II.HDV-I(Diasome) is now in Phase III.The technologies of the above-mentioned products are summarized.For oral insulin delivery,enteric-coating is always adopted to protect insulin from acidic denaturation in the stomach.Absorption enhancers such as SNAC and sodium caprate are the mostcommonly used strategy to enhance the bioavailability of insulin.However,despite the large dose of the absorption enhancers,the oral bioavailability of insulin is still limited to 1-2%.Also,the safety of long-term use of the absorption enhancers remains to be evaluated.The challenges of oral insulin administration are mainly from the physiological barriers in the gastrointestinal tract,including acidic environment in the stomach,enzymatic degradation,mucus barrier and poor intestinal epithelial permeation.Nevertheless,the rapid development of nanotechnology has created huge opportunities.Our group studied deeply into the design and development of two distinct ligand modified nanoparticles based on the diabetic intestinal microenvironment and intestinal bile acid pathway.On one hand,folic acid modified chitosan nanoparticles(FNP) were developed to target the upregulated folate receptors and transporters in the diabetic intestinal microenvironment.The cellular uptake and transcellular transport of insulin were enhanced due to the receptor mediated pathway of FNP.The relative bioavailability of FNP in diabetic rats was about 9.5%.On the other hand,deoxycholic acid modified nanoparticles(DNP) were devised to target the intestinal bile acid pathway.In vivo absorption studies further revealed that the relative bioavailability of DNP was about 15.9%.In conclusion,the intestinal epithelium is critical to the oral absorption of insulin.Designing novel active-targeted drug delivery systems can efficiently improve the oral absorption of insulin. |
| 会议录 | 2016年中国药物制剂大会、中国药学会药剂专业委员会2016年学术年会、中国化学制药工业协会固体制剂专业委员会2016年工作年会、国际控释协会中国分会2016年学术年会会议论文集
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| 文献子类 | Article |
| 语种 | 英语 |
| 资助项目 | the “Science and technology innovation action plan for basic research” of Shanghai[14JC1493200] ; Institutes for Drug Discovery and Development,Chinese Academy of Sciences[CASIMM0120153020] |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/267014]  |
| 专题 | 药物制剂研究中心 |
| 作者单位 | 中国科学院上海药物研究所,药物制剂研究中心,上海 201203, 中国. |
| 推荐引用方式 GB/T 7714 | Gan Y. Challenges and strategies of oral insulin delivery[C]. 见:. |
入库方式： OAI收割
来源：上海药物研究所
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