A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Engineered Multifunctional Albumin-Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin
Tekijät: 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
Kustantaja: WILEY-V C H VERLAG GMBH
Julkaisuvuosi: 2018
Journal: Small
Tietokannassa oleva lehden nimi: SMALL
Lehden akronyymi: SMALL
Artikkelin numero: ARTN 1800462
Vuosikerta: 14
Numero: 27
Sivujen määrä: 11
ISSN: 1613-6810
eISSN: 1613-6829
DOI: https://doi.org/10.1002/smll.201800462
Tiivistelmä
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.
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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