Engineered Multifunctional Albumin‐Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin |
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| Authors: | João P Martins Roberto D'Auria Dongfei Liu Flavia Fontana Mónica P A Ferreira Alexandra Correia Marianna Kemell Karina Moslova Ermei Mäkilä Jarno Salonen Luca Casettari Jouni Hirvonen Bruno Sarmento Hélder A Santos |
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| Affiliation: | 1. Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland;2. Department of Biomolecular Sciences, School of Pharmacy, University of Urbino, Urbino, (PU), Italy;3. Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland;4. Department of Chemistry, University of Helsinki, Helsinki, Finland;5. Department of Physics and Astronomy, University of Turku, Turku, Finland;6. i3S – Instituto de Investiga??o e Inova??o em Saúde, University of Porto, Porto, Portugal;7. INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal;8. CESPU – Instituto de Investiga??o e Forma??o Avan?ada em Ciências e Tecnologias da Saúde, Gandra, Portugal |
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| Abstract: | The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection‐based delivery of insulin. Neonatal Fc receptor (FcRn)‐mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn‐targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH‐responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH‐sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn‐targeted NPs. Overall, these FcRn‐targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin. |
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| Keywords: | albumin FcRn insulin nanoparticles porous silicon |
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