淀粉受体激动剂普兰林肽的口服给药

IF 1.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Peptide Science Pub Date : 2024-01-31 DOI:10.1002/pep2.24346

Celimar Sinézia, Tháyna Sisnande, Luis Peña Icart, Luís Maurício T. R. Lima

{"title":"淀粉受体激动剂普兰林肽的口服给药","authors":"Celimar Sinézia, Tháyna Sisnande, Luis Peña Icart, Luís Maurício T. R. Lima","doi":"10.1002/pep2.24346","DOIUrl":null,"url":null,"abstract":"Amylin receptor agonism safely benefit diabetic patients, reducing the insulin requirements and glycemic excursions. Pramlintide is the triple proline human amylin analogue first used as injectable drug, but lacking physico-chemical compatibility when co-formulated with insulin. Here, we report the design and characterization of polymeric microparticles for oral delivery of pramlintide. Eudragit S100, a gastric-resistant polymer, was used in preparation of pramlintide-loaded spherical microcapsules by double emulsion and solvent evaporation technique, with approximately 66 μm ± 11 particle size, with 83.2% ± 2.7 efficiency for pramlintide entrapment and 67.6% ± 2.1 yield. Intra-venous pramlintide free in solution showed a plasmatic half-life of 6.8 min in mice. In contrast, oral delivery of acid-resistant pramlintide-loaded microparticles in mice showed a protracted release for 120 min compared to 30 min obtained for pramlintide in solution. Our data provide evidences for the potential use of the oral route in the therapeutic development of pramlintide formulations.","PeriodicalId":19825,"journal":{"name":"Peptide Science","volume":"50 1","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oral delivery of the amylin receptor agonist pramlintide\",\"authors\":\"Celimar Sinézia, Tháyna Sisnande, Luis Peña Icart, Luís Maurício T. R. Lima\",\"doi\":\"10.1002/pep2.24346\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Amylin receptor agonism safely benefit diabetic patients, reducing the insulin requirements and glycemic excursions. Pramlintide is the triple proline human amylin analogue first used as injectable drug, but lacking physico-chemical compatibility when co-formulated with insulin. Here, we report the design and characterization of polymeric microparticles for oral delivery of pramlintide. Eudragit S100, a gastric-resistant polymer, was used in preparation of pramlintide-loaded spherical microcapsules by double emulsion and solvent evaporation technique, with approximately 66 μm ± 11 particle size, with 83.2% ± 2.7 efficiency for pramlintide entrapment and 67.6% ± 2.1 yield. Intra-venous pramlintide free in solution showed a plasmatic half-life of 6.8 min in mice. In contrast, oral delivery of acid-resistant pramlintide-loaded microparticles in mice showed a protracted release for 120 min compared to 30 min obtained for pramlintide in solution. Our data provide evidences for the potential use of the oral route in the therapeutic development of pramlintide formulations.\",\"PeriodicalId\":19825,\"journal\":{\"name\":\"Peptide Science\",\"volume\":\"50 1\",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-01-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Peptide Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/pep2.24346\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Peptide Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/pep2.24346","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

淀粉受体激动剂可安全地使糖尿病患者受益，减少胰岛素需求量和血糖波动。普兰林肽是三重脯氨酸人淀粉样蛋白类似物，最初用作注射药物，但与胰岛素共同配制时缺乏物理化学兼容性。在此，我们报告了用于口服普兰林肽的聚合物微粒的设计和特性。采用双乳化和溶剂蒸发技术，利用耐胃聚合物 Eudragit S100 制备了负载普兰林肽的球形微胶囊，粒径约为 66 μm ± 11，普兰林肽的包封效率为 83.2% ± 2.7，产率为 67.6% ± 2.1。静脉注射游离于溶液中的普拉克林肽在小鼠体内的血浆半衰期为 6.8 分钟。相比之下，在小鼠体内口服抗酸普兰林肽微颗粒后，普兰林肽的释放时间延长了 120 分钟，而溶液中的普兰林肽的释放时间仅为 30 分钟。我们的数据为口服途径在普兰林肽制剂的治疗开发中的潜在应用提供了证据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Oral delivery of the amylin receptor agonist pramlintide

查看原文本刊更多论文

Oral delivery of the amylin receptor agonist pramlintide

Amylin receptor agonism safely benefit diabetic patients, reducing the insulin requirements and glycemic excursions. Pramlintide is the triple proline human amylin analogue first used as injectable drug, but lacking physico-chemical compatibility when co-formulated with insulin. Here, we report the design and characterization of polymeric microparticles for oral delivery of pramlintide. Eudragit S100, a gastric-resistant polymer, was used in preparation of pramlintide-loaded spherical microcapsules by double emulsion and solvent evaporation technique, with approximately 66 μm ± 11 particle size, with 83.2% ± 2.7 efficiency for pramlintide entrapment and 67.6% ± 2.1 yield. Intra-venous pramlintide free in solution showed a plasmatic half-life of 6.8 min in mice. In contrast, oral delivery of acid-resistant pramlintide-loaded microparticles in mice showed a protracted release for 120 min compared to 30 min obtained for pramlintide in solution. Our data provide evidences for the potential use of the oral route in the therapeutic development of pramlintide formulations.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Peptide Science Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

5.20

自引率

4.20%

发文量

期刊介绍： The aim of Peptide Science is to publish significant original research papers and up-to-date reviews covering the entire field of peptide research. Peptide Science provides a forum for papers exploring all aspects of peptide synthesis, materials, structure and bioactivity, including the use of peptides in exploring protein functions and protein-protein interactions. By incorporating both experimental and theoretical studies across the whole spectrum of peptide science, the journal serves the interdisciplinary biochemical, biomaterials, biophysical and biomedical research communities. Peptide Science is the official journal of the American Peptide Society.