{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:22:50Z","timestamp":1784658170431,"version":"3.55.0"},"reference-count":101,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Controlled Release"],"published-print":{"date-parts":[[2014,7]]},"DOI":"10.1016\/j.jconrel.2014.04.042","type":"journal-article","created":{"date-parts":[[2014,5,6]],"date-time":"2014-05-06T18:52:06Z","timestamp":1399402326000},"page":"11-21","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":55,"special_numbering":"C","title":["Particle designs for the stabilization and controlled-delivery of protein drugs by biopolymers: A case study on insulin"],"prefix":"10.1016","volume":"186","author":[{"given":"Hui-Peng","family":"Lim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beng-Ti","family":"Tey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng-Seng","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jconrel.2014.04.042_bb0005","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrd1695","article-title":"Protein drug stability: a formulation challenge","volume":"4","author":"Frokjaer","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0010","series-title":"IDF Diabetes Atlas","author":"I.D. Federation","year":"2013"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0015","first-page":"141","article-title":"Pancreatic extracts in the treatment of diabetes mellitus","volume":"12","author":"Banting","year":"1922","journal-title":"Can. Med. Assoc. J."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0020","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3109\/10611860903302815","article-title":"Design of oral insulin delivery systems","volume":"18","author":"Wong","year":"2010","journal-title":"J. Drug Target."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0025","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1517\/17425247.5.4.403","article-title":"Developments in polymeric devices for oral insulin delivery","volume":"5","author":"Babu","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0030","series-title":"Patenting Nanomedicines","first-page":"345","article-title":"Chitosan and Alginate Nanoparticles as Oral Insulin Carrier","author":"Wong","year":"2012"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0035","first-page":"1552","article-title":"Recent advances in insulin delivery systems: an update","volume":"11","author":"Nitesh","year":"2010","journal-title":"World Appl. Sci. J."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0040","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/BF02867128","article-title":"Oral insulin-fact or fiction?","volume":"8","author":"Gowthamarajan","year":"2003","journal-title":"Resonance"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0045","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.progpolymsci.2012.04.004","article-title":"Strategies for effective oral insulin delivery with modified chitosan nanoparticles: a review","volume":"37","author":"Mukhopadhyay","year":"2012","journal-title":"Prog. Polym. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0050","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1046\/j.1464-5491.2003.01076.x","article-title":"Alternative routes of insulin delivery","volume":"20","author":"Owens","year":"2003","journal-title":"Diabet. Med."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0055","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/S1262-3636(06)72804-X","article-title":"Alternatives routes of insulin delivery","volume":"32","author":"Lassmann-Vague","year":"2006","journal-title":"Diabetes Metab."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0060","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ijpharm.2006.12.019","article-title":"Preparation of dual crosslinked alginate\u2013chitosan blend gel beads and in vitro controlled release in oral site-specific drug delivery system","volume":"336","author":"Xu","year":"2007","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0065","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.drudis.2012.03.019","article-title":"An overview of natural polymers for oral insulin delivery","volume":"17","author":"Sonia","year":"2012","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0070","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1136\/gut.29.8.1035","article-title":"Measurement of gastrointestinal pH profiles in normal ambulant human subjects","volume":"29","author":"Evans","year":"1988","journal-title":"Gut"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0075","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/jps.2600840604","article-title":"Absorption characteristics of chemically modified-insulin derivatives with various fatty acids in the small and large intestine","volume":"84","author":"Asada","year":"1995","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0080","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1002\/jps.22560","article-title":"Oral delivery system for two-pulse colonic release of protein drugs and protease inhibitor\/absorption enhancer compounds","volume":"100","author":"Del Curto","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0085","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.jconrel.2013.05.002","article-title":"A permeation enhancer for increasing transport of therapeutic macromolecules across the intestine","volume":"172","author":"Gupta","year":"2013","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0090","doi-asserted-by":"crossref","first-page":"2801","DOI":"10.1016\/j.biomaterials.2011.12.038","article-title":"Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery","volume":"33","author":"Su","year":"2012","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0095","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1211\/0022357022052","article-title":"Potential utility of various protease inhibitors for improving the intestinal absorption of insulin in rats","volume":"55","author":"Liu","year":"2003","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0100","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1023\/A:1007696723125","article-title":"Design and in vivo evaluation of an oral delivery system for insulin","volume":"17","author":"Marsch\u00fctz","year":"2000","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0105","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jconrel.2004.03.008","article-title":"Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption","volume":"97","author":"Morishita","year":"2004","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0110","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.carbpol.2011.04.070","article-title":"Lectin-functionalized carboxymethylated kappa-carrageenan microparticles for oral insulin delivery","volume":"86","author":"Leong","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0115","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.jconrel.2007.05.019","article-title":"Effective oral delivery of insulin in animal models using vitamin B12-coated dextran nanoparticles","volume":"122","author":"Chalasani","year":"2007","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0120","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0378-5173(01)00579-8","article-title":"Liposomes with phosphatidylethanol as a carrier for oral delivery of insulin: studies in the rat","volume":"216","author":"Kisel","year":"2001","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0125","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0378-5173(97)00237-8","article-title":"Oral delivery of insulin by using surface coating liposomes: improvement of stability of insulin in GI tract","volume":"157","author":"Iwanaga","year":"1997","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0130","first-page":"966","article-title":"Hypoglycemic efficacy of chitosan-coated insulin liposomes after oral administration in mice","volume":"25","author":"Wu","year":"2004","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0135","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1023\/A:1016009313548","article-title":"Enteral absorption of insulin in rats from mucoadhesive chitosan-coated liposomes","volume":"13","author":"Takeuchi","year":"1996","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0140","first-page":"743","article-title":"Oral insulin delivery by means of solid lipid nanoparticles","volume":"2","author":"Sarmento","year":"2007","journal-title":"Int. J. Nanomedicine"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0145","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jconrel.2012.11.005","article-title":"Polymeric hydrogels for oral insulin delivery","volume":"165","author":"Chaturvedi","year":"2013","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0150","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1517\/17425247.5.1.45","article-title":"Nanoparticle strategies for the oral delivery of insulin","volume":"5","author":"Damg\u00e9","year":"2008","journal-title":"Expert Opin. Drug Deliv."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0155","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0168-3659(99)00247-3","article-title":"Nanosphere based oral insulin delivery","volume":"65","author":"Carino","year":"2000","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0160","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3390\/polym3031377","article-title":"Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier","volume":"3","author":"Makadia","year":"2011","journal-title":"Polymers"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0165","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.jconrel.2005.02.025","article-title":"Stability of insulin during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres","volume":"106","author":"Ibrahim","year":"2005","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0170","series-title":"Biodegradable Polymers as Drug Delivery Systems","author":"Langer","year":"1990"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0175","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1248\/cpb.44.235","article-title":"Instability of bovine insulin in poly(lactide-co-glycolide)(PLGA) microspheres","volume":"44","author":"Uchida","year":"1996","journal-title":"Chem. Pharm. Bull."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0180","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1211\/0022357021778448","article-title":"Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers","volume":"54","author":"P\u00e9rez","year":"2002","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0185","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0168-3659(03)00328-6","article-title":"Polymer degradation and in vitro release of a model protein from poly(d, l-lactide-<i>co<\/i>\u2212glycolide) nano-and microparticles","volume":"92","author":"Panyam","year":"2003","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0190","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1023\/A:1007582911958","article-title":"Visual evidence of acidic environment within degrading poly(lactic-co-glycolic acid) (PLGA) microspheres","volume":"17","author":"Fu","year":"2000","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0195","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/jps.20625","article-title":"BSA degradation under acidic conditions: a model for protein instability during release from PLGA delivery systems","volume":"95","author":"Estey","year":"2006","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0200","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1177\/193229681300700228","article-title":"Oral insulin delivery: how far are we?","volume":"7","author":"Fonte","year":"2013","journal-title":"J. Diabetes Sci. Technol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0205","series-title":"Effectiveness of Oral Insulin in Unstable Type 1 Diabetes Patients","author":"Hadassah Medical Organization","year":"2000"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0210","series-title":"Diabetes Technology Meeting","article-title":"Extended Exposure to an Oral Insulin Formulation Yields Decreased Insulin Secretion in Type II Diabetes Subjects","author":"Kidron","year":"2010"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0215","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1463-1326.2009.01146.x","article-title":"The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetes","volume":"12","author":"Luzio","year":"2010","journal-title":"Diabetes Obes. Metab."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0220","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.jcis.2009.05.027","article-title":"Prediction models for shape and size of ca-alginate macrobeads produced through extrusion-dripping method","volume":"338","author":"Chan","year":"2009","journal-title":"J. Colloid Interface Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0225","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0022-2836(02)00021-9","article-title":"Insulin at pH2: structural analysis of the conditions promoting insulin fibre formation","volume":"318","author":"Whittingham","year":"2002","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0230","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1021\/bi00901a005","article-title":"The labile amide in insulin: preparation of desalanine-desamido-insulin*","volume":"2","author":"Slobin","year":"1963","journal-title":"Biochem. J."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0235","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1016\/S0021-9258(19)70830-8","article-title":"Separation and characterization of acid-induced insulin transformation products by paper electrophoresis in 7m urea","volume":"237","author":"Sundby","year":"1962","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0240","doi-asserted-by":"crossref","first-page":"11171","DOI":"10.1021\/bi0507940","article-title":"Thermal dissociation and unfolding of insulin","volume":"44","author":"Huus","year":"2005","journal-title":"Biochem. J."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0245","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1023\/A:1013334916162","article-title":"In situ study of insulin aggregation induced by water-organic solvent interface","volume":"18","author":"Kwon","year":"2001","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0250","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0169-409X(98)00075-1","article-title":"Oral insulin delivery","volume":"35","author":"Carino","year":"1999","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0255","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2042-7158.1991.tb05437.x","article-title":"The effect of site of administration in the gastrointestinal tract on the absorption of insulin from nanocapsules in diabetic rats","volume":"43","author":"Michel","year":"1991","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0260","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2005.10.050","article-title":"Alginate microspheres prepared by internal gelation: development and effect on insulin stability","volume":"311","author":"Silva","year":"2006","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0265","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1002\/jps.10149","article-title":"Formulation pH modulates the interaction of insulin with chitosan nanoparticles","volume":"91","author":"Ma","year":"2002","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0270","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2006.04.017","article-title":"Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan \u2014 a review","volume":"114","author":"George","year":"2006","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0275","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0378-5173(92)90353-4","article-title":"In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers","volume":"78","author":"Lehr","year":"1992","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0280","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1007\/s11095-005-8175-y","article-title":"Uptake and transport of PEG-graft-trimethyl-chitosan copolymer-insulin nanocomplexes by epithelial cells","volume":"22","author":"Mao","year":"2005","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0285","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.1002\/app.32979","article-title":"Bioadhesive hydrophobic chitosan microparticles for oral delivery of insulin: in vitro characterization and in vivo uptake studies","volume":"119","author":"Sonia","year":"2011","journal-title":"J. Appl. Polym. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0290","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1080\/02652040500162220","article-title":"Preparation and in vitro evaluation of thiolated chitosan microparticles","volume":"22","author":"Maculotti","year":"2005","journal-title":"J. Microencapsul."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0295","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.jconrel.2009.01.011","article-title":"Synthesis and evaluation of lauryl succinyl chitosan particles towards oral insulin delivery and absorption","volume":"135","author":"Rekha","year":"2009","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0300","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.addr.2012.09.012","article-title":"Thermosensitive sol\u2013gel reversible hydrogels","volume":"64","author":"Jeong","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0305","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ijbiomac.2013.03.064","article-title":"Oral delivery of insulin from alginate\/chitosan crosslinked by glutaraldehyde","volume":"58","author":"Tahtat","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0310","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1081\/BIO-120004343","article-title":"Encapsulation of insulin in chitosan-coated alginate beads: oral therapeutic peptide delivery","volume":"30","author":"\u00d6nal","year":"2002","journal-title":"Artif. Cells Blood Substit. Immobil. Biotechnol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0315","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.jconrel.2004.10.032","article-title":"Bioadhesive interaction and hypoglycemic effect of insulin-loaded lectin-microparticle conjugates in oral insulin delivery system","volume":"102","author":"Kim","year":"2005","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0320","doi-asserted-by":"crossref","first-page":"250","DOI":"10.3109\/02652048.2011.646329","article-title":"Novel alginate gel microspheres produced by impinging aerosols for oral delivery of proteins","volume":"29","author":"Hariyadi","year":"2012","journal-title":"J. Microencapsul."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0325","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.carbpol.2006.02.008","article-title":"Characterization of insulin-loaded alginate nanoparticles produced by ionotropic pre-gelation through DSC and FTIR studies","volume":"66","author":"Sarmento","year":"2006","journal-title":"Carbohydr. Polym."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0330","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1016\/j.actbio.2009.03.007","article-title":"Colloidal carrier integrating biomaterials for oral insulin delivery: influence of component formulation on physicochemical and biological parameters","volume":"5","author":"Woitiski","year":"2009","journal-title":"Acta Biomater."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0335","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s10989-005-9010-3","article-title":"Development and comparison of different nanoparticulate polyelectrolyte complexes as insulin carriers","volume":"12","author":"Sarmento","year":"2006","journal-title":"Int. J. Pept. Res. Ther."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0340","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1007\/s11095-007-9367-4","article-title":"Alginate\/chitosan nanoparticles are effective for oral insulin delivery","volume":"24","author":"Sarmento","year":"2007","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0345","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ejps.2006.06.008","article-title":"Insulin encapsulation in reinforced alginate microspheres prepared by internal gelation","volume":"29","author":"Silva","year":"2006","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0350","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.colsurfb.2006.05.006","article-title":"Preparation and characterization of uniform-sized chitosan microspheres containing insulin by membrane emulsification and a two-step solidification process","volume":"50","author":"Wang","year":"2006","journal-title":"Colloids Surf. B: Biointerfaces"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0355","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ejpb.2010.09.016","article-title":"Preparation and evaluation of alginate-chitosan microspheres for oral delivery of insulin","volume":"77","author":"Zhang","year":"2011","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0360","first-page":"23","article-title":"Nanoemulsions coated with alginate\/chitosan as oral insulin delivery systems: preparation, characterization, and hypoglycemic effect in rats","volume":"8","author":"Li","year":"2013","journal-title":"Int. J. Nanomedicine"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0365","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.carbpol.2007.02.012","article-title":"Insulin-loaded alginate microspheres for oral delivery-effect of polysaccharide reinforcement on physicochemical properties and release profile","volume":"69","author":"Martins","year":"2007","journal-title":"Carbohydr. Polym."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0370","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0378-5173(02)00486-6","article-title":"Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo","volume":"249","author":"Pan","year":"2002","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0375","first-page":"1","article-title":"Calcium alginate nanocarriers as possible vehicles for oral delivery of insulin","author":"Goswami","year":"2012","journal-title":"J. Exp. Nanosci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0380","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.ejps.2010.12.007","article-title":"Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery","volume":"42","author":"Makhlof","year":"2011","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0385","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1021\/bm0607776","article-title":"Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery","volume":"8","author":"Lin","year":"2007","journal-title":"Biomacromolecules"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0390","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1081\/DDC-120030930","article-title":"Insulin-loaded calcium pectinate nanoparticles: effects of pectin molecular weight and formulation pH","volume":"30","author":"Cheng","year":"2004","journal-title":"Drug Dev. Ind. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0395","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/10601320903458556","article-title":"Designing gelatin nanocarriers as a swellable system for controlled release of insulin: an in-vitro kinetic study","volume":"47","author":"Goswami","year":"2009","journal-title":"J. Macromol. Sci. A"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0400","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1080\/10717540801905165","article-title":"Polyelectrolyte biomaterial interactions provide nanoparticulate carrier for oral insulin delivery","volume":"15","author":"Reis","year":"2008","journal-title":"Drug Deliv."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0405","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.ejps.2006.12.007","article-title":"Nanoparticulate delivery system for insulin: Design, characterization and in vitro\/in vivo bioactivity","volume":"30","author":"Reis","year":"2007","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0410","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2298\/CICEQ0601040S","article-title":"Insulin release from alginate microspheres reinforced with dextran sulfate","volume":"12","author":"Silva","year":"2006","journal-title":"Chem. Ind. Chem. Eng. Q."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0415","first-page":"1","article-title":"Efficacy of mucoadhesive hydrogel microparticles of whey protein and alginate for oral insulin delivery","author":"D\u00e9at-Lain\u00e9","year":"2012","journal-title":"Pharm. Res."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0420","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1002\/(SICI)1097-4628(19960314)59:11<1795::AID-APP16>3.0.CO;2-T","article-title":"Chitosan\/calcium-alginate beads for oral delivery of insulin","volume":"59","author":"Hari","year":"1996","journal-title":"J. Appl. Polym. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0425","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1248\/cpb.57.663","article-title":"Calcium pectinate gel bead intended for oral protein delivery: preparation improvement and formulation development","volume":"57","author":"Si","year":"2009","journal-title":"Chem. Pharm. Bull."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0430","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1080\/026520400405660","article-title":"Lipoinsulin encapsulated alginate-chitosan capsules: intestinal delivery in diabetic rats","volume":"17","author":"Ramadas","year":"2000","journal-title":"J. Microencapsul."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0435","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.ijpharm.2009.04.031","article-title":"Facile fabrication of well-defined hydrogel beads with magnetic nanocomposite shells","volume":"376","author":"Liu","year":"2009","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0440","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1080\/00222348.2013.789306","article-title":"Facile preparation of core-shell nanocomposite microgels","volume":"53","author":"Liu","year":"2014","journal-title":"J. Macromol. Sci. B"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0445","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.procbio.2012.01.018","article-title":"Synthesis and characterization of alginate coated zinc calcium phosphate nanoparticles for intestinal delivery of insulin","volume":"47","author":"Paul","year":"2012","journal-title":"Process Biochem."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0450","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.colsurfb.2006.09.012","article-title":"Development and characterization of new insulin containing polysaccharide nanoparticles","volume":"53","author":"Sarmento","year":"2006","journal-title":"Colloids Surf. B: Biointerfaces"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0455","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.nano.2008.01.003","article-title":"Preparation and characterization of insulin nanoparticles using chitosan and its quaternized derivatives","volume":"4","author":"Bayat","year":"2008","journal-title":"Nanomedicine"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0460","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1081\/PDT-100100513","article-title":"Porcine insulin biodegradable polyester microspheres: stability and in vitro release characteristics","volume":"5","author":"Shao","year":"2000","journal-title":"Pharm. Dev. Technol."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0465","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/S0142-9612(98)00073-8","article-title":"Microcapsules of alginate-chitosan-I: a quantitative study of the interaction between alginate and chitosan","volume":"19","author":"G\u00e5ser\u00f8d","year":"1998","journal-title":"Biomaterials"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0470","doi-asserted-by":"crossref","first-page":"5290","DOI":"10.1002\/jps.21347","article-title":"Nanoparticulate biopolymers deliver insulin orally eliciting pharmacological response","volume":"97","author":"Reis","year":"2008","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0475","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1002\/(SICI)1097-4628(19970103)63:1<125::AID-APP13>3.0.CO;2-4","article-title":"Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers","volume":"63","author":"Calvo","year":"1997","journal-title":"J. Appl. Polym. Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0480","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1126\/science.1074868","article-title":"Colloidosomes: selectively permeable capsules composed of colloidal particles","volume":"298","author":"Dinsmore","year":"2002","journal-title":"Science"},{"key":"10.1016\/j.jconrel.2014.04.042_bb0485","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1002\/adma.200800918","article-title":"Double emulsion-templated nanoparticle colloidosomes with selective permeability","volume":"20","author":"Lee","year":"2008","journal-title":"Adv. Mater."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0490","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1039\/b411359d","article-title":"Fabrication of novel colloidosome microcapsules with gelled aqueous cores","volume":"14","author":"Cayre","year":"2004","journal-title":"J. Mater. Chem."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0495","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S1359-0294(02)00008-0","article-title":"Particles as surfactants-similarities and differences","volume":"7","author":"Binks","year":"2002","journal-title":"Curr. Opin. Colloid Interface Sci."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0500","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0378-5173(92)90088-J","article-title":"The controlled release of blue dextran from alginate beads","volume":"79","author":"Kim","year":"1992","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.jconrel.2014.04.042_bb0505","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1007\/s10856-010-4073-x","article-title":"Acyl modified chitosan derivatives for oral delivery of insulin and curcumin","volume":"21","author":"Shelma","year":"2010","journal-title":"J. Mater. Sci. Mater. Med."}],"container-title":["Journal of Controlled Release"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365914002752?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365914002752?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,4,3]],"date-time":"2022-04-03T05:12:53Z","timestamp":1648962773000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168365914002752"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7]]},"references-count":101,"alternative-id":["S0168365914002752"],"URL":"https:\/\/doi.org\/10.1016\/j.jconrel.2014.04.042","relation":{},"ISSN":["0168-3659"],"issn-type":[{"value":"0168-3659","type":"print"}],"subject":[],"published":{"date-parts":[[2014,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Particle designs for the stabilization and controlled-delivery of protein drugs by biopolymers: A case study on insulin","name":"articletitle","label":"Article Title"},{"value":"Journal of Controlled Release","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jconrel.2014.04.042","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2014 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}]}}