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Repeated daily injections of subcutaneous insulin is the standard treatment for patients with type 1 diabetes mellitus; however, subcutaneous insulin injections can potentially cause local discomfort, patient noncompliance, hypoglycemia, failure to regulate glucose homeostasis, infections, and fat deposits at the injection sites. In recent years, numerous attempts have been made to produce safe and efficient nanoparticles for oral insulin delivery. Oral administration is considered the most effective alternative route to insulin injection, but it is accompanied by several challenges related to enzymatic proteolysis, digestive breakdown, and absorption barriers. A number of natural and synthetic polymeric, lipid\u2010based, and inorganic nanoparticles have been investigated for use. Although improvements have recently been made in potential oral insulin delivery systems, these require further investigation before clinical trials are conducted. In this review, new approaches to oral insulin delivery for diabetes treatment are discussed, including polymeric, lipid\u2010based, and inorganic nanoparticles, as well as the clinical trials performed for this purpose.<\/jats:p>","DOI":"10.1002\/ddr.21903","type":"journal-article","created":{"date-parts":[[2021,12,3]],"date-time":"2021-12-03T01:54:47Z","timestamp":1638496487000},"page":"301-316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Novel strategies to oral delivery of insulin: Current progress of nanocarriers for diabetes management"],"prefix":"10.1002","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1254-0894","authenticated-orcid":false,"given":"Adel","family":"Abdel\u2010Moneim","sequence":"first","affiliation":[{"name":"Molecular Physiology Division, Faculty of Science Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa","family":"Ramadan","sequence":"additional","affiliation":[{"name":"Histology and Molecular Cytology Division, Zoology Department, Faculty of Science Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2020.116441"},{"key":"e_1_2_11_3_1","first-page":"2","article-title":"Recombinant human insulin\u2010PLGA NP administrated orally after combination with a protease inhibitor (N\u2010Ethylmaleimide): In vivo results","volume":"7","author":"Abdelkadera D. 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