{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:09:22Z","timestamp":1784657362301,"version":"3.55.0"},"reference-count":40,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100012246","name":"Priority Academic Program Development of Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["jpharmsci.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pharmaceutical Sciences"],"published-print":{"date-parts":[[2021,1]]},"DOI":"10.1016\/j.xphs.2020.07.004","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T23:28:19Z","timestamp":1594510099000},"page":"268-279","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":46,"title":["Design and Investigation of Penetrating Mechanism of Octaarginine-Modified Alginate Nanoparticles for Improving Intestinal Insulin Delivery"],"prefix":"10.1016","volume":"110","author":[{"given":"Manman","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusheng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liefeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.xphs.2020.07.004_bib1","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.biomaterials.2017.10.022","article-title":"Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery","volume":"151","author":"Fan","year":"2018","journal-title":"Biomaterials"},{"key":"10.1016\/j.xphs.2020.07.004_bib2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.addr.2016.01.010","article-title":"Oral delivery of macromolecular drugs: where we are after almost 100 years of attempts","volume":"101","author":"Moroz","year":"2016","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.xphs.2020.07.004_bib3","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.addr.2016.06.005","article-title":"Intestinal permeation enhancers for oral peptide delivery","volume":"106","author":"Maher","year":"2016","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.xphs.2020.07.004_bib4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.addr.2016.02.004","article-title":"Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials","volume":"106","author":"Aguirre","year":"2016","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.xphs.2020.07.004_bib5","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jconrel.2017.09.003","article-title":"Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment","volume":"264","author":"Wong","year":"2017","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.xphs.2020.07.004_bib6","first-page":"294","article-title":"PH-sensitive peptide hydrogel for glucose-responsive insulin delivery","volume":"51","author":"Li","year":"2017","journal-title":"Acta Mater"},{"key":"10.1016\/j.xphs.2020.07.004_bib7","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.jconrel.2018.07.045","article-title":"Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin","volume":"286","author":"Presas","year":"2018","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.xphs.2020.07.004_bib8","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.eurpolymj.2017.05.015","article-title":"Preparation of polyurethane\u2013alginate\/chitosan core shell nanoparticles for the purpose of oral insulin delivery","volume":"92","author":"Aditi","year":"2017","journal-title":"Eur Polym J"},{"key":"10.1016\/j.xphs.2020.07.004_bib9","first-page":"1","article-title":"Effect of polyethylene glycol on bis(2-hydroxyethyl) terephthalate-based polyurethane\/alginate ph-sensitive blend for oral protein delivery","volume":"35","author":"Aditi","year":"2016","journal-title":"Adv Polym Technol"},{"key":"10.1016\/j.xphs.2020.07.004_bib10","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1016\/j.ijbiomac.2017.05.062","article-title":"Evaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin","volume":"103","author":"Aluani","year":"2017","journal-title":"Int J Biol Macromol"},{"key":"10.1016\/j.xphs.2020.07.004_bib11","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.foodchem.2017.02.071","article-title":"Development of a nutraceutical nano-delivery system through emulsification\/internal gelation of alginate","volume":"229","author":"Mokhtari","year":"2017","journal-title":"Food Chem"},{"key":"10.1016\/j.xphs.2020.07.004_bib12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/bcpt.12342","article-title":"Mucus as a barrier to drug delivery\u2013understanding and mimicking the barrier properties","volume":"116","author":"Boegh","year":"2015","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1016\/j.xphs.2020.07.004_bib13","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.bmcl.2016.11.083","article-title":"Intelligent substance delivery into cells using cell-penetrating peptides","volume":"27","author":"Tashima","year":"2017","journal-title":"Bioorg Med Chem Lett"},{"key":"10.1016\/j.xphs.2020.07.004_bib14","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.addr.2015.02.008","article-title":"Delivery of therapeutic oligonucleotides with cell penetrating peptides","volume":"87","author":"Boisgu\u00e9rin","year":"2015","journal-title":"Adv Drug Deliv Rev"},{"key":"10.1016\/j.xphs.2020.07.004_bib15","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1021\/ar200256e","article-title":"Efficient intracellular delivery of nucleic acid pharmaceuticals using cell- penetrating peptides","volume":"45","author":"Nakase","year":"2012","journal-title":"Acc Chem Res"},{"key":"10.1016\/j.xphs.2020.07.004_bib16","first-page":"373","article-title":"Recent in\u00a0vivo advances in cell-penetrating peptide-assisted drug delivery. Expert Opin","volume":"13","author":"Kurrikoff","year":"2016","journal-title":"Drug Deliv"},{"key":"10.1016\/j.xphs.2020.07.004_bib17","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ijpharm.2013.03.033","article-title":"Oligoarginine-modified biodegradable nanoparticles improve the intestinal absorption of insulin","volume":"448","author":"Liu","year":"2013","journal-title":"Int J Pharm"},{"key":"10.1016\/j.xphs.2020.07.004_bib18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jconrel.2004.10.018","article-title":"Cationic TAT peptide transduction domain enters cells by micropinocytosis","volume":"102","author":"Kaplan","year":"2005","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.xphs.2020.07.004_bib19","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1016\/j.ymthe.2004.08.010","article-title":"Cellular uptake of arginine-rich peptides: roles for macropinocytosis and actin rearrangement","volume":"10","author":"Ikuhiko","year":"2004","journal-title":"Mol Ther"},{"key":"10.1016\/j.xphs.2020.07.004_bib20","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1021\/bc700289w","article-title":"Cellular internalization and distribution of arginine-rich peptides as a function of extracellular peptide concentration, serum, and plasma membrane associated proteoglycans","volume":"19","author":"Kosuge","year":"2008","journal-title":"Bioconjug Chem"},{"key":"10.1016\/j.xphs.2020.07.004_bib21","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jconrel.2016.04.012","article-title":"Dual chitosan\/albumin-coated alginate\/dextran sulfate nanoparticles for enhanced oral delivery of insulin","volume":"232","author":"Lopes","year":"2016","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.xphs.2020.07.004_bib22","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.carbpol.2017.06.061","article-title":"A\u00a0cell-penetrating peptide mediated chitosan nanocarriers for improving intestinal insulin delivery","volume":"174","author":"Li","year":"2017","journal-title":"Carbohydr Polym"},{"key":"10.1016\/j.xphs.2020.07.004_bib23","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.biologicals.2017.06.002","article-title":"Nano-encapsulation of chicken immunoglobulin (IgY) in sodium alginate nanoparticles: in\u00a0vitro characterization","volume":"49","author":"Mostafa","year":"2017","journal-title":"Biologicals"},{"key":"10.1016\/j.xphs.2020.07.004_bib24","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1039\/C8FO00883C","article-title":"Artificial sweetener saccharin disrupts intestinal epithelial cells' barrier function in\u00a0vitro","volume":"9","author":"Santos","year":"2018","journal-title":"Food Funct"},{"key":"10.1016\/j.xphs.2020.07.004_bib25","doi-asserted-by":"crossref","first-page":"15430","DOI":"10.1021\/acsami.5b03555","article-title":"N-trimethyl chitosan chloride-coated PLGA nanoparticles overcoming multiple barriers to oral insulin absorption","volume":"7","author":"Sheng","year":"2015","journal-title":"ACS Appl Mater Interfaces"},{"key":"10.1016\/j.xphs.2020.07.004_bib26","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.carbpol.2016.10.021","article-title":"Mechanism of surface charge triggered intestinal epithelial tight junction opening upon chitosan nanoparticles for insulin oral delivery","volume":"157","author":"Wang","year":"2017","journal-title":"Carbohydr Polym"},{"key":"10.1016\/j.xphs.2020.07.004_bib27","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.biomaterials.2011.10.075","article-title":"Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport","volume":"33","author":"Jin","year":"2012","journal-title":"Biomaterials"},{"key":"10.1016\/j.xphs.2020.07.004_bib28","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jconrel.2017.12.034","article-title":"Design and intestinal mucus, penetration mechanism of core-shell nanocomplex","volume":"272","author":"Zhang","year":"2018","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.xphs.2020.07.004_bib29","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":"Bruno","year":"2006","journal-title":"Carbohydr Polym"},{"key":"10.1016\/j.xphs.2020.07.004_bib30","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.reactfunctpolym.2017.08.015","article-title":"Controlled delivery of oral insulin aspart using pH-responsive alginate\/\u03ba- carrageenan composite hydrogel beads","volume":"120","author":"Lim","year":"2017","journal-title":"React Funct Polym"},{"key":"10.1016\/j.xphs.2020.07.004_bib31","first-page":"107","article-title":"TEER measurement techniques for in\u00a0vitro barrier model systems","volume":"20","author":"Srinivasan","year":"2015","journal-title":"J\u00a0Lab Autom"},{"key":"10.1016\/j.xphs.2020.07.004_bib32","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1021\/bm049312a","article-title":"Preparation of nanoparticles composed of chitosan\/poly-\u00e7-glutamic acid and evaluation of their permeability through caco-2 cells","volume":"6","author":"Lin","year":"2005","journal-title":"Biomacromolecules"},{"key":"10.1016\/j.xphs.2020.07.004_bib33","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.ijbiomac.2018.01.077","article-title":"A\u00a0cell-penetrating peptide conjugated carboxymethyl-\u03b2-cyclodextrin to improve intestinal absorption of insulin","volume":"111","author":"Yang","year":"2018","journal-title":"Int J Biol Macromol"},{"key":"10.1016\/j.xphs.2020.07.004_bib34","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20090042","article-title":"Low concentration thresholds of plasma membranes for rapid energy-independent translocation of a cell-penetrating peptide","volume":"420","author":"Watkins","year":"2009","journal-title":"Biochem J"},{"key":"10.1016\/j.xphs.2020.07.004_bib35","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1248\/cpb.c16-00505","article-title":"Current understanding of direct translocation of arginine-rich cell-penetrating peptides and its internalization mechanisms","volume":"64","author":"Takeuchi","year":"2016","journal-title":"Chem Pharm Bull"},{"key":"10.1016\/j.xphs.2020.07.004_bib36","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1096\/fasebj.6.12.1381691","article-title":"Nitric oxides as a secretory product of mammalian cells","volume":"6","author":"Nathan","year":"1992","journal-title":"FASEB J"},{"key":"10.1016\/j.xphs.2020.07.004_bib37","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jconrel.2005.05.017","article-title":"Nitric oxide donors can enhance the intestinal transport and absorption of insulin and [Asu1,7]-eel calcitonin in rats","volume":"106","author":"Fetih","year":"2005","journal-title":"J\u00a0Control Release"},{"key":"10.1016\/j.xphs.2020.07.004_bib38","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.niox.2017.01.003","article-title":"Nitrite increases glucose-stimulated insulin secretion and islet insulin content in obese type 2 diabetic male rats","volume":"64","author":"Sevda","year":"2017","journal-title":"Nitric Oxide"},{"key":"10.1016\/j.xphs.2020.07.004_bib39","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.ejps.2013.05.013","article-title":"Characteristics of reversible absorption-enhancing effect of sodium nitroprusside in rat small intestine","volume":"49","author":"Yusuke","year":"2013","journal-title":"Eur J Pharm Sci"},{"key":"10.1016\/j.xphs.2020.07.004_bib40","first-page":"590","article-title":"Hypoglycemic effects of sodium alginate-insulin nanoparticles on the blood glucose level of streptozotocin-induced diabetic Wistar rats","volume":"30","author":"Dong","year":"2005","journal-title":"Med J Chin PLA"}],"container-title":["Journal of Pharmaceutical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235492030366X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235492030366X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T09:29:57Z","timestamp":1758360597000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002235492030366X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["S002235492030366X"],"URL":"https:\/\/doi.org\/10.1016\/j.xphs.2020.07.004","relation":{},"ISSN":["0022-3549"],"issn-type":[{"value":"0022-3549","type":"print"}],"subject":[],"published":{"date-parts":[[2021,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design and Investigation of Penetrating Mechanism of Octaarginine-Modified Alginate Nanoparticles for Improving Intestinal Insulin Delivery","name":"articletitle","label":"Article Title"},{"value":"Journal of Pharmaceutical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.xphs.2020.07.004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 American Pharmacists Association\u00ae. Published by Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}