Rujing Xu, Ying Lu, Mengxiao Liu, Yanzhao Yin, Junsheng Zhao, Lin Wu* and Song Shen*,
{"title":"通过在聚山梨醇酯-80 微胶囊中负载增强胰岛素的口服给药效果","authors":"Rujing Xu, Ying Lu, Mengxiao Liu, Yanzhao Yin, Junsheng Zhao, Lin Wu* and Song Shen*, ","doi":"10.1021/acsanm.4c0426210.1021/acsanm.4c04262","DOIUrl":null,"url":null,"abstract":"<p >Oral delivery of insulin exhibits low bioavailability due to the hydrolysis in acidic gastric juice, biodegradation of enzymes, and inefficient penetration through the intestinal mucus and epithelial cell layer. Here, we report a micelle platform to enhance the oral delivery of insulin. Insulin was precipitated by zinc ions to form hydrophobic nanoparticles and subsequently coated with a surfactant polysorbate-80 (Tween-80) to form nanosized micelles (TW-Zn-rhINS). Tween-80 protects the insulin from the degradation of enzymes, meanwhile facilitating the diffusion within mucus and the epithelial cell layer by opening the tight junctions. The micelles were then lyophilized and encapsulated in enteric capsules to overcome acidic hydrolysis in gastric juice. The micelles significantly increased transcellular insulin transport and uptake. The in vivo experiments demonstrated that oral TW-Zn-rhINS micelle capsules (30 IU/kg) decreased the blood glucose of diabetic mice by 58.74% after administration for 6 h, while the postprandial blood glucose dropped by 51.1%. Pharmacokinetics data indicated that the relative oral bioavailability of TW-Zn-rhINS was 7.88%, which was 7.73 times higher than that of insulin. The micelles present a promising platform to enhance the oral bioavailability of insulin, also indicating a potential for oral delivery of protein.</p>","PeriodicalId":6,"journal":{"name":"ACS Applied Nano Materials","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enhanced Oral Delivery of Insulin via Loading in Polysorbate-80 Micelles\",\"authors\":\"Rujing Xu, Ying Lu, Mengxiao Liu, Yanzhao Yin, Junsheng Zhao, Lin Wu* and Song Shen*, \",\"doi\":\"10.1021/acsanm.4c0426210.1021/acsanm.4c04262\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Oral delivery of insulin exhibits low bioavailability due to the hydrolysis in acidic gastric juice, biodegradation of enzymes, and inefficient penetration through the intestinal mucus and epithelial cell layer. Here, we report a micelle platform to enhance the oral delivery of insulin. Insulin was precipitated by zinc ions to form hydrophobic nanoparticles and subsequently coated with a surfactant polysorbate-80 (Tween-80) to form nanosized micelles (TW-Zn-rhINS). Tween-80 protects the insulin from the degradation of enzymes, meanwhile facilitating the diffusion within mucus and the epithelial cell layer by opening the tight junctions. The micelles were then lyophilized and encapsulated in enteric capsules to overcome acidic hydrolysis in gastric juice. The micelles significantly increased transcellular insulin transport and uptake. The in vivo experiments demonstrated that oral TW-Zn-rhINS micelle capsules (30 IU/kg) decreased the blood glucose of diabetic mice by 58.74% after administration for 6 h, while the postprandial blood glucose dropped by 51.1%. Pharmacokinetics data indicated that the relative oral bioavailability of TW-Zn-rhINS was 7.88%, which was 7.73 times higher than that of insulin. The micelles present a promising platform to enhance the oral bioavailability of insulin, also indicating a potential for oral delivery of protein.</p>\",\"PeriodicalId\":6,\"journal\":{\"name\":\"ACS Applied Nano Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Nano Materials\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsanm.4c04262\",\"RegionNum\":2,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Nano Materials","FirstCategoryId":"88","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsanm.4c04262","RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, MULTIDISCIPLINARY","Score":null,"Total":0}
Enhanced Oral Delivery of Insulin via Loading in Polysorbate-80 Micelles
Oral delivery of insulin exhibits low bioavailability due to the hydrolysis in acidic gastric juice, biodegradation of enzymes, and inefficient penetration through the intestinal mucus and epithelial cell layer. Here, we report a micelle platform to enhance the oral delivery of insulin. Insulin was precipitated by zinc ions to form hydrophobic nanoparticles and subsequently coated with a surfactant polysorbate-80 (Tween-80) to form nanosized micelles (TW-Zn-rhINS). Tween-80 protects the insulin from the degradation of enzymes, meanwhile facilitating the diffusion within mucus and the epithelial cell layer by opening the tight junctions. The micelles were then lyophilized and encapsulated in enteric capsules to overcome acidic hydrolysis in gastric juice. The micelles significantly increased transcellular insulin transport and uptake. The in vivo experiments demonstrated that oral TW-Zn-rhINS micelle capsules (30 IU/kg) decreased the blood glucose of diabetic mice by 58.74% after administration for 6 h, while the postprandial blood glucose dropped by 51.1%. Pharmacokinetics data indicated that the relative oral bioavailability of TW-Zn-rhINS was 7.88%, which was 7.73 times higher than that of insulin. The micelles present a promising platform to enhance the oral bioavailability of insulin, also indicating a potential for oral delivery of protein.
期刊介绍:
ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.