{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T02:25:53Z","timestamp":1786242353561,"version":"build-2736575974"},"reference-count":100,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T00:00:00Z","timestamp":1710720000000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/144719\/2019"],"award-info":[{"award-number":["SFRH\/BD\/144719\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wires.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["WIREs Nanomed Nanobiotechnol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Type 2 diabetes <jats:italic>mellitus<\/jats:italic> (T2DM) is a metabolic disorder that arises when the body cannot respond fully to insulin, leading to impaired glucose tolerance. Currently, the treatment embraces non\u2010pharmacological actions (e.g., diet and exercise) co\u2010associated with the administration of antidiabetic drugs. Metformin is the first\u2010line treatment for T2DM; nevertheless, alternative therapeutic strategies involving glucagon\u2010like peptide\u20101 (GLP\u20101) analogs have been explored for managing the disease. GLP\u20101 analogs trigger insulin secretion and suppress glucagon release in a glucose\u2010dependent manner thereby, reducing the risk of hyperglycemia. Additionally, GLP\u20101 analogs have an extended plasma half\u2010life compared to the endogenous peptide due to their high resistance to degradation by dipeptidyl peptidase\u20104. However, GLP\u20101 analogs are mainly administered via subcutaneous route, which can be inconvenient for the patients. Even considering an oral delivery approach, GLP\u20101 analogs are exposed to the harsh conditions of the gastrointestinal tract (GIT) and the intestinal barriers (mucus and epithelium). Hereupon, there is an unmet need to develop non\u2010invasive oral transmucosal drug delivery strategies, such as the incorporation of GLP\u20101 analogs into nanoplatforms, to overcome the GIT barriers. Nanotechnology has the potential to shield antidiabetic peptides against the acidic pH and enzymatic activity of the stomach. In addition, the nanoparticles can be coated and\/or surface\u2010conjugated with mucodiffusive polymers and target intestinal ligands to improve their transport through the intestinal mucus and epithelium. This review focuses on the main hurdles associated with the oral administration of GLP\u20101 and GLP\u20101 analogs, and the nanosystems developed to improve the oral bioavailability of the antidiabetic peptides.<\/jats:p><jats:p>This article is categorized under:<jats:list list-type=\"simple\">\n<jats:list-item><jats:p>Therapeutic Approaches and Drug Discovery &gt; Nanomedicine for Infectious Disease<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Nanotechnology Approaches to Biology &gt; Nanoscale Systems in Biology<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p>","DOI":"10.1002\/wnan.1952","type":"journal-article","created":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T06:16:52Z","timestamp":1710829012000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["New insights into nanomedicines for oral delivery of <scp>glucagon\u2010like<\/scp> peptide\u20101 analogs"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3171-8122","authenticated-orcid":false,"given":"Soraia Filipa Tavares","family":"Pinto","sequence":"first","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S) University of Porto  Porto Portugal"},{"name":"Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar (ICBAS) University of Porto  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7850-6309","authenticated-orcid":false,"given":"H\u00e9lder Almeida","family":"Santos","sequence":"additional","affiliation":[{"name":"Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy University of Helsinki  Helsinki Finland"},{"name":"W.J. Kolff Institute for Biomedical Engineering and Materials Science University Medical Center Groningen, University of Groningen  Groningen The Netherlands"},{"name":"Department of Biomedical Engineering University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5763-7553","authenticated-orcid":false,"given":"Bruno Filipe Carmelino Cardoso","family":"Sarmento","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S) University of Porto  Porto Portugal"},{"name":"Instituto Universit\u00e1rio de Ci\u00eancias da Sa\u00fade (IUCS\u2010CESPU)  Gandra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,3,18]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2019.04.022"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.9b00308"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40005-013-0072-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01499-w"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13361"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmatsci.2017.05.001"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/193229681200600630"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/c6nr00294c"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5b02762"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2014.07.026"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.04.016"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.9.2492"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.017"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.07.051"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01743-9"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-020-00619-0"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-2081"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.05.007"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.2015.1068288"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-019-0156-6"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar7047"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-015-0143-4"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700781"},{"issue":"8","key":"e_1_2_12_25_1","first-page":"503","article-title":"Lixisenatide, a novel GLP\u20101 receptor agonist for the treatment of type 2 diabetes mellitus","volume":"12","author":"Christensen M.","year":"2009","journal-title":"Investigational Drug Journal"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14831"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.5.1187"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2011.0050"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0053-0"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101351"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(08)61206-4"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.12.009"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.2165\/11585880-000000000-00000"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107519"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00178"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12850"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1067"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3109\/10717544.2013.819611"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.111625"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.114097"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2012.07.063"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.2337\/ds16-0026"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2006"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11030129"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118067598.ch1"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2017.08.010"},{"key":"e_1_2_12_47_1","first-page":"14","volume-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2021"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2017.03.015"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2020.04.025"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-015-0343-6"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/la5047047"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-020-00894-y"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05715-4"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118833322.ch2"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00155"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021545"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00726"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-014-1513-1"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1080\/10717544.2021.2023704"},{"key":"e_1_2_12_60_1","unstructured":"Lily E.(n.d.).Prescribing information sheet of Trulicity\u00ae (dulaglutide). Available from:https:\/\/pi.lilly.com\/us\/trulicity-uspi.pdf. Accessed from: 22ndJanuary 2024."},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.24238"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.110.034066"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.8b20821"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.140"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-020-00981-0"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-017-1086-7"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.123"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14496"},{"key":"e_1_2_12_69_1","unstructured":"Novo Nordisk. (n.d.).Rybelsus\u00ae (semaglutide) tablets for oral use. Available from:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/213051s000lbl.pdf. Accessed 28thMay 28 2023"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2016.1192130"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c00637"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.2147\/ijn.S30013"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2021.120583"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1039\/c9na00308h"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.7573\/dic.212585"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0709"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-0366"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)01324-6"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2020.101513"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.08.088"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-19170-y"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1177\/0885328220947889"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0169-409x(97)00048-3"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2016.04.024"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b00809"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.2217\/nnm-2018-0322"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.progpolymsci.2014.07.010"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.09.012"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.09.012"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2016.86"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1016639"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa863"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11020078"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2019.102132"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021479"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12479"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120209"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319146"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1080\/1061186x.2018.1455839"},{"key":"e_1_2_12_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2018.05.055"},{"key":"e_1_2_12_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2017.151"}],"container-title":["WIREs Nanomedicine and Nanobiotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/wnan.1952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T08:26:23Z","timestamp":1714119983000},"score":1,"resource":{"primary":{"URL":"https:\/\/wires.onlinelibrary.wiley.com\/doi\/10.1002\/wnan.1952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":100,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/wnan.1952"],"URL":"https:\/\/doi.org\/10.1002\/wnan.1952","archive":["Portico"],"relation":{},"ISSN":["1939-5116","1939-0041"],"issn-type":[{"value":"1939-5116","type":"print"},{"value":"1939-0041","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"assertion":[{"value":"2023-08-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-18","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1952"}}