{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T17:18:20Z","timestamp":1764350300570,"version":"build-2065373602"},"reference-count":45,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T00:00:00Z","timestamp":1460937600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"crossref","award":["252215","281300"],"award-info":[{"award-number":["252215","281300"]}],"id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Helsinki Research Funds"},{"name":"Biocentrum Helsinki"},{"name":"European Research Council","award":["310892"],"award-info":[{"award-number":["310892"]}]},{"name":"North Portugal Regional Operational Programme"},{"DOI":"10.13039\/501100003125","name":"Finnish Cultural Foundation","doi-asserted-by":"crossref","award":["00150869"],"award-info":[{"award-number":["00150869"]}],"id":[{"id":"10.13039\/501100003125","id-type":"DOI","asserted-by":"crossref"}]},{"name":"FCT","award":["SFRH\/BD\/87016\/2012","SFRH\/BD\/90404\/2012"],"award-info":[{"award-number":["SFRH\/BD\/87016\/2012","SFRH\/BD\/90404\/2012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Adv Funct Materials"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>During the last decades, advanced oral delivery systems to enhance the intestinal absorption of widely applicable proteins and peptides, particularly insulin, have been developed. Here, chitosan\u2010conjugated undecylenic acid\u2010modified thermally hydrocarbonized porous silicon nanoparticles (CSUn NPs) are used, which promote the mucoadhesion and cellular interactions, thus boosting the intestinal permeability of insulin. Then, to further potentiate the mucoadhesion and permeability enhancement of chitosan\u2010modified NPs, the surface of the NPs is further modified with either <jats:sc>l<\/jats:sc>\u2010cysteine (CYS\u2010CSUn NPs) or a cell\u2010penetrating peptide (CPP\u2010CSUn NPs). CYS\u2010CSUn and CPP\u2010CSUn NPs show 17\u2010 and 12\u2010fold increase in the apparent permeability of insulin across cellular intestinal cells, respectively, with significant enhancement in the cellular interactions. The insulin uptake mechanism pathways in intestinal cells from the developed NPs are also unraveled, which demonstrates major involvement of active transport process and electrostatic interactions, along with adsorptive and clathrin\u2010mediated endocytic pathways. Moreover, after oral administration in diabetic rats, CYS\u2010CSUn NPs show 1.86\u2010 and 2.03\u2010fold increase in the relative bioavailability of insulin, as compared to empty NPs and oral insulin solution, respectively. In conclusion, this study presents <jats:sc>l<\/jats:sc>\u2010cysteine modified CSUn NPs as a promising strategy with the ability to overcome the multiple barriers for oral delivery of insulin.<\/jats:p>","DOI":"10.1002\/adfm.201505252","type":"journal-article","created":{"date-parts":[[2016,4,18]],"date-time":"2016-04-18T03:30:00Z","timestamp":1460950200000},"page":"3405-3416","source":"Crossref","is-referenced-by-count":100,"title":["Thiolation and Cell\u2010Penetrating Peptide Surface Functionalization of Porous Silicon Nanoparticles for Oral Delivery of Insulin"],"prefix":"10.1002","volume":"26","author":[{"given":"Neha","family":"Shrestha","sequence":"first","affiliation":[{"name":"Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki  FI\u201000014 Finland"}]},{"given":"Francisca","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki  FI\u201000014 Finland"},{"name":"I3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB \u2212 Instituto de Engenharia Biom\u00e9 dica Universidade do Porto  Rua Alfredo Allen 208 4200\u2010135 Porto Portugal"},{"name":"ICBAS \u2013 Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar University of Porto  Rua de Jorge Viterbo Ferreira 4050\u2013313 Porto Portugal"}]},{"given":"Mohammad\u2010Ali","family":"Shahbazi","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki  FI\u201000014 Finland"}]},{"given":"Ermei","family":"M\u00e4kil\u00e4","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki  FI\u201000014 Finland"},{"name":"Laboratory of Industrial Physics Department of Physics and Astronomy University of Turku  FI\u201020014 Finland"}]},{"given":"Maria Jo\u00e3o","family":"Gomes","sequence":"additional","affiliation":[{"name":"I3S \u2013 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade and INEB \u2212 Instituto de Engenharia Biom\u00e9 dica Universidade do Porto  Rua Alfredo Allen 208 4200\u2010135 Porto Portugal"},{"name":"ICBAS \u2013 Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar University of Porto  Rua de Jorge Viterbo Ferreira 4050\u2013313 Porto Portugal"}]},{"given":"B\u00e1rbara","family":"Herranz\u2010Blanco","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki  FI\u201000014 Finland"}]},{"given":"Rici","family":"Lindgren","sequence":"additional","affiliation":[{"name":"Laboratory of Industrial Physics Department of Physics and Astronomy University of Turku  FI\u201020014 Finland"}]},{"given":"Sari","family":"Granroth","sequence":"additional","affiliation":[{"name":"Materials Physics Laboratory Department of 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