{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:25:23Z","timestamp":1772227523030,"version":"3.50.1"},"reference-count":49,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,15]],"date-time":"2020-01-15T00:00:00Z","timestamp":1579046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Polyelectrolyte nanocomposites rarely reach a stable state and aggregation often occurs. Here, we report the synthesis of nanocomposites for the oral delivery of insulin composed of alginate, dextran sulfate, poly-(ethylene glycol) 4000, poloxamer 188, chitosan, and bovine serum albumin. The nanocomposites were obtained by Ca2+-induced gelation of alginate followed by an electrostatic-interaction process among the polyelectrolytes. Chitosan seemed to be essential for the final size of the nanocomposites and there was an optimal content that led to the synthesis of nanocomposites of 400\u2013600 nm hydrodynamic size. The enhanced stability of the synthesized nanocomposites was assessed with LUMiSizer after synthesis. Nanocomposite stability over time and under variations of ionic strength and pH were assessed with dynamic light scattering. The rounded shapes of nanocomposites were confirmed by scanning electron microscopy. After loading with insulin, analysis by HPLC revealed complete drug release under physiologically simulated conditions.<\/jats:p>","DOI":"10.3390\/md18010055","type":"journal-article","created":{"date-parts":[[2020,1,17]],"date-time":"2020-01-17T04:14:41Z","timestamp":1579234481000},"page":"55","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Complex Polysaccharide-Based Nanocomposites for Oral Insulin Delivery"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3976-8925","authenticated-orcid":false,"given":"Mar","family":"Collado-Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK"},{"name":"Department of Pharmaceutical technology, Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Maria Cristina","family":"Ferreri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical technology, Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"given":"Alessandra R.","family":"Freitas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical technology, Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-6000","authenticated-orcid":false,"given":"Ana Cl\u00e1udia","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical technology, Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"REQUIMTE\/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9587-682X","authenticated-orcid":false,"given":"Nuno R.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-7654","authenticated-orcid":false,"given":"Guzm\u00e1n","family":"Carissimi","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Murcia, 30100 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3654-3862","authenticated-orcid":false,"given":"Joana A. D.","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical technology, Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8473-1190","authenticated-orcid":false,"given":"F. Guillermo","family":"D\u00edaz Ba\u00f1os","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, University of Murcia, 30100 Murcia, Spain"}]},{"given":"Gloria","family":"Villora","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, University of Murcia, 30100 Murcia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-0068","authenticated-orcid":false,"given":"Francisco","family":"Veiga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical technology, Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"REQUIMTE\/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-8944","authenticated-orcid":false,"given":"Antonio","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical technology, Faculty of Pharmacy of the University of Coimbra, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1021\/bm049786+","article-title":"Versatile and Efficient Formation of Colloids of Biopolymer-Based Polyelectrolyte Complexes","volume":"5","author":"Schatz","year":"2004","journal-title":"Biomacromolecules"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.ijbiomac.2014.08.040","article-title":"pH-sensitive chitosan\/alginate core-shell nanoparticles for efficient and safe oral insulin delivery","volume":"72","author":"Mukhopadhyay","year":"2015","journal-title":"Int. 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