Muzi Li, Nan Wang, Ruiyuan Liu, Xinyue Zhang, Wei He, Wen Zhang, Jiaxin Li, Chen Peng, Yan Li
{"title":"pH 和 H2O2 双敏感纳米颗粒可实现更强、更安全的葡萄糖反应性口服胰岛素给药,用于糖尿病治疗","authors":"Muzi Li, Nan Wang, Ruiyuan Liu, Xinyue Zhang, Wei He, Wen Zhang, Jiaxin Li, Chen Peng, Yan Li","doi":"10.7150/thno.98177","DOIUrl":null,"url":null,"abstract":"<b>Background:</b> Oral insulin delivery is considered a revolutionary alternative to daily subcutaneous injection. However, the oral bioavailability of insulin is very low due to the poor oral absorption into blood circulation./n<b>Methods:</b> To promote penetration across the intestinal epithelium and achieve enhanced and safe glucose-responsive oral insulin delivery, pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive nanoparticles (NPs) were constructed. The NPs were loaded of glucose oxidase (GOx) and insulin by pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive amphiphilic polymer incorporated with phenylboronic ester-conjugated poly(2-hydroxyethyl methacrylate) and poly(carboxybetaine) (PCB). The dual-sensitive NPs were utilized for the treatment of type 1 diabetes mellitus (T1DM) after oral administration./n<b>Results:</b> The dual-sensitive NPs could enhance the transport of insulin across the intestinal epithelium into blood facilitated by zwitterionic PCB. By virtue of the generated low pH and high H<sub>2</sub>O<sub>2</sub> with GOx in hyperglycemic environment, the pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive NPs were disassembled to achieve rapid and sustained release of insulin. After oral administration of the dual-sensitive NPs in enteric capsules into T1DM mouse model, the oral bioavailability of insulin reached 20.24%, and the NPs achieved hypoglycemic effect for a few hours longer than subcutaneously injected insulin. Importantly, the pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive NPs could ameliorate the local decline of pH and rise of H<sub>2</sub>O<sub>2</sub> to avoid the toxic side effect./n<b>Conclusion:</b> Therefore, this work would provide a promising platform for the enhanced and safe treatment of diabetes mellitus.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"pH and H2O2 dual-sensitive nanoparticles enable enhanced and safe glucose-responsive oral insulin delivery for diabetes mellitus treatment\",\"authors\":\"Muzi Li, Nan Wang, Ruiyuan Liu, Xinyue Zhang, Wei He, Wen Zhang, Jiaxin Li, Chen Peng, Yan Li\",\"doi\":\"10.7150/thno.98177\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<b>Background:</b> Oral insulin delivery is considered a revolutionary alternative to daily subcutaneous injection. However, the oral bioavailability of insulin is very low due to the poor oral absorption into blood circulation./n<b>Methods:</b> To promote penetration across the intestinal epithelium and achieve enhanced and safe glucose-responsive oral insulin delivery, pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive nanoparticles (NPs) were constructed. The NPs were loaded of glucose oxidase (GOx) and insulin by pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive amphiphilic polymer incorporated with phenylboronic ester-conjugated poly(2-hydroxyethyl methacrylate) and poly(carboxybetaine) (PCB). The dual-sensitive NPs were utilized for the treatment of type 1 diabetes mellitus (T1DM) after oral administration./n<b>Results:</b> The dual-sensitive NPs could enhance the transport of insulin across the intestinal epithelium into blood facilitated by zwitterionic PCB. By virtue of the generated low pH and high H<sub>2</sub>O<sub>2</sub> with GOx in hyperglycemic environment, the pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive NPs were disassembled to achieve rapid and sustained release of insulin. After oral administration of the dual-sensitive NPs in enteric capsules into T1DM mouse model, the oral bioavailability of insulin reached 20.24%, and the NPs achieved hypoglycemic effect for a few hours longer than subcutaneously injected insulin. Importantly, the pH and H<sub>2</sub>O<sub>2</sub> dual-sensitive NPs could ameliorate the local decline of pH and rise of H<sub>2</sub>O<sub>2</sub> to avoid the toxic side effect./n<b>Conclusion:</b> Therefore, this work would provide a promising platform for the enhanced and safe treatment of diabetes mellitus.\",\"PeriodicalId\":22932,\"journal\":{\"name\":\"Theranostics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.4000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Theranostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/thno.98177\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.98177","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
pH and H2O2 dual-sensitive nanoparticles enable enhanced and safe glucose-responsive oral insulin delivery for diabetes mellitus treatment
Background: Oral insulin delivery is considered a revolutionary alternative to daily subcutaneous injection. However, the oral bioavailability of insulin is very low due to the poor oral absorption into blood circulation./nMethods: To promote penetration across the intestinal epithelium and achieve enhanced and safe glucose-responsive oral insulin delivery, pH and H2O2 dual-sensitive nanoparticles (NPs) were constructed. The NPs were loaded of glucose oxidase (GOx) and insulin by pH and H2O2 dual-sensitive amphiphilic polymer incorporated with phenylboronic ester-conjugated poly(2-hydroxyethyl methacrylate) and poly(carboxybetaine) (PCB). The dual-sensitive NPs were utilized for the treatment of type 1 diabetes mellitus (T1DM) after oral administration./nResults: The dual-sensitive NPs could enhance the transport of insulin across the intestinal epithelium into blood facilitated by zwitterionic PCB. By virtue of the generated low pH and high H2O2 with GOx in hyperglycemic environment, the pH and H2O2 dual-sensitive NPs were disassembled to achieve rapid and sustained release of insulin. After oral administration of the dual-sensitive NPs in enteric capsules into T1DM mouse model, the oral bioavailability of insulin reached 20.24%, and the NPs achieved hypoglycemic effect for a few hours longer than subcutaneously injected insulin. Importantly, the pH and H2O2 dual-sensitive NPs could ameliorate the local decline of pH and rise of H2O2 to avoid the toxic side effect./nConclusion: Therefore, this work would provide a promising platform for the enhanced and safe treatment of diabetes mellitus.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.