Details

Autor(en) / Beteiligte

• Martins, João P.
• D'Auria, Roberto
• Liu, Dongfei
• Fontana, Flavia
• Ferreira, Mónica P. A.
• Correia, Alexandra
• Kemell, Marianna
• Moslova, Karina
• Mäkilä, Ermei
• Salonen, Jarno
• Casettari, Luca
• Hirvonen, Jouni
• Sarmento, Bruno
• Santos, Hélder A.

Titel

Engineered Multifunctional Albumin‐Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin

Ist Teil von

• Small (Weinheim an der Bergstrasse, Germany), 2018-07, Vol.14 (27), p.e1800462-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Quelle

Wiley-Blackwell Full Collection

Beschreibungen/Notizen

• 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. Insulin‐loaded albumin‐conjugated porous silicon nanoparticles encapsulate into pH‐sensitive polymer. The formulation shows tunable size and size distribution, morphology, high cytocompatibility, and controlled drug release profile. Insulin permeation across the intestinal epithelium is higher when loaded into albumin‐decorated nanoparticles. The nanoparticles hijack the FcRn transcytotic pathway, and cross the epithelial cell layer, improving insulin delivery.