{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:23:14Z","timestamp":1768810994315,"version":"3.49.0"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1107836, GNT1146627, GNT1143296"],"award-info":[{"award-number":["GNT1107836, GNT1146627, GNT1143296"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Type 2 diabetes makes up approximately 85% of all diabetic cases and it is linked to approximately one-third of all hospitalisations. Newer therapies with long-acting biologics such as glucagon-like peptide-1 (GLP-1) analogues have been promising in managing the disease, but they cannot reverse the pathology of the disease. Additionally, their parenteral administration is often associated with high healthcare costs, risk of infections, and poor patient adherence associated with phobia of needles. Oral delivery of these compounds would significantly improve patient compliance; however, poor enzymatic stability and low permeability across the gastrointestinal tract makes this task challenging. In the present work, large pore dendritic silica nanoparticles (DSNPs) with a pore size of ~10 nm were prepared, functionalized, and optimized in order to achieve high peptide loading and improve intestinal permeation of exenatide, a GLP-1 analogue. Compared to the loading capacity of the most popular, Mobil Composition of Matter No. 41 (MCM-41) with small pores, DSNPs showed significantly high loading owing to their large and dendritic pore structure. Among the tested DSNPs, pristine and phosphonate-modified DSNPs (PDSNPs) displayed remarkable loading of 40 and 35% w\/w, respectively. Furthermore, particles successfully coated with positively charged chitosan reduced the burst release of exenatide at both pH 1.2 and 6.8. Compared with free exenatide, both chitosan-coated and uncoated PDSNPs enhanced exenatide transport through the Caco-2 monolayer by 1.7 fold. Interestingly, when a triple co-culture model of intestinal permeation was used, chitosan-coated PDSNPs performed better compared to both PDSNPs and free exenatide, which corroborated our hypothesis behind using chitosan to interact with mucus and improve permeation. These results indicate the emerging role of large pore silica nanoparticles as promising platforms for oral delivery of biologics such as exenatide.<\/jats:p>","DOI":"10.3390\/pharmaceutics11080418","type":"journal-article","created":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T06:10:14Z","timestamp":1566195014000},"page":"418","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Rationally Designed Dendritic Silica Nanoparticles for Oral Delivery of Exenatide"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1004-0351","authenticated-orcid":false,"given":"Muhammad Mustafa","family":"Abeer","sequence":"first","affiliation":[{"name":"School of Pharmacy, The University of Queensland, Brisbane QLD 4072, Australia"}]},{"given":"Anand Kumar","family":"Meka","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Queensland, Brisbane QLD 4072, Australia"}]},{"given":"Naisarg","family":"Pujara","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Queensland, Brisbane QLD 4072, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-7148","authenticated-orcid":false,"given":"Tushar","family":"Kumeria","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Queensland, Brisbane QLD 4072, Australia"},{"name":"Mater Research Institute\u2014The University of Queensland, Translational Research Institute, Woolloongabba QLD 4102, Australia"}]},{"given":"Ekaterina","family":"Strounina","sequence":"additional","affiliation":[{"name":"Center for Advanced Imaging, The University of Queensland, Brisbane QLD 4072, Australia"}]},{"given":"Rute","family":"Nunes","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"Instituto de Engenharia Biom\u00e9dica (INEB), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}]},{"given":"Ana","family":"Costa","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"Instituto de Engenharia Biom\u00e9dica (INEB), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5763-7553","authenticated-orcid":false,"given":"Bruno","family":"Sarmento","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (I3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"Instituto de Engenharia Biom\u00e9dica (INEB), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal"},{"name":"CESPU, Instituto de Investiga\u00e7\u00e3o e Forma\u00e7\u00e3o Avan\u00e7ada em Ci\u00eancias e Tecnologias da Sa\u00fade, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal"}]},{"given":"Sumaira Z.","family":"Hasnain","sequence":"additional","affiliation":[{"name":"Mater Research Institute\u2014The University of Queensland, Translational Research Institute, Woolloongabba QLD 4102, Australia"},{"name":"Australian Infectious Disease Research Centre\u2014The University of Queensland Building 76 Room 155 Cooper Road, St. Lucia QLD 4067, Australia"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-8484","authenticated-orcid":false,"given":"Benjamin P.","family":"Ross","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Queensland, Brisbane QLD 4072, Australia"}]},{"given":"Amirali","family":"Popat","sequence":"additional","affiliation":[{"name":"School of Pharmacy, The University of Queensland, Brisbane QLD 4072, Australia"},{"name":"Mater Research Institute\u2014The University of Queensland, Translational Research Institute, Woolloongabba QLD 4102, Australia"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. 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