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To overcome the inherent poor stability of peptide and protein therapeutics, stereocomplexation of the peptide, insulin, is applied, onto D\u2010PLA\u2010PEG in aqueous media. Nanoparticles of \u2248400\u00a0nm are spontaneously formed when water\u2010soluble D configured PLA\u2010PEG diblock copolymer and L\u2010 configured insulin interlock into a stereocomplex, owing to their concave convex fitness. In vitro release of insulin from stereocomplex in phosphate buffer solution (PBS) pH 7.4 solution shows sustained release for 14 weeks. The therapeutic efficacy of the PLA\u2010insulin stereocomplex nanoparticles are evaluated in diabetic Akita mice. Blood glucose levels and body weight are closely monitored for a period of 17\u00a0weeks, revealing a significant reduction in glucose levels of the Akita mice treated with insulin stereocomplex, as well as normal body weight gain. These findings suggest that the stereocomplex nanoparticles of insulin\u2010D\u2010PLA\u2010PEG present a promising and effective sustained and extended release platform for insulin. Notably, the use of water\u2010soluble D\u2010PLA\u2010PEG for stereocomplexation in water expands the applicability of this approach to fabricate controlled delivery systems for peptide and protein therapeutics.<\/jats:p>","DOI":"10.1002\/mabi.202300497","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T20:28:55Z","timestamp":1701289735000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Insulin Extended Release from PLA\u2010PEG Stereocomplex Nanoparticles"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0599-9653","authenticated-orcid":false,"given":"Tovi","family":"Shapira\u2010Furman","sequence":"first","affiliation":[{"name":"The Hebrew University of Jerusalem Faculty of Medicine School of Pharmacy  Jerusalem 91120 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-7726","authenticated-orcid":false,"given":"Abraham J.","family":"Domb","sequence":"additional","affiliation":[{"name":"The Hebrew University of Jerusalem Faculty of Medicine School of Pharmacy  Jerusalem 91120 Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-59990-3_3"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12055"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2016.06.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/2210296504666140402235024"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3109\/03639040902939213"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00396-016-4002-8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2016.07.004"},{"key":"e_1_2_8_8_1","first-page":"47","volume":"7","author":"Fattahi F.","year":"2019","journal-title":"Poly(lactic acid) (PLA) Nanofibers for Bone Tissue Engineering"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3900(200110)175:1<105::AID-MASY105>3.0.CO;2-C"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/ma951144e"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/polyeng-2014-0175"},{"key":"e_1_2_8_12_1","first-page":"175","volume":"16","author":"Nahhas A. 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