Neonatal Fc receptor-targeted lignin-encapsulated porous silicon nanoparticles for enhanced cellular interactions and insulin permeation across the intestinal epithelium.
| Autor: | Martins JP; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Figueiredo P; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Wang S; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Espo E; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Celi E; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.; Department of Pharmacy, University of Chieti - Pescara 'G d'Annunzio', I-66100, Chieti, Italy., Martins B; Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Kemell M; Department of Chemistry, University of Helsinki, FI-00014, Helsinki, Finland., Moslova K; Department of Chemistry, University of Helsinki, FI-00014, Helsinki, Finland., Mäkilä E; Department of Physics and Astronomy, University of Turku, FI-20014, Turku, Finland., Salonen J; Department of Physics and Astronomy, University of Turku, FI-20014, Turku, Finland., Kostiainen MA; Biohybrid Materials, Department of Bioproducts and Biosystems, Aalto University, FI-00076, Aalto, Finland., Celia C; Department of Pharmacy, University of Chieti - Pescara 'G d'Annunzio', I-66100, Chieti, Italy., Cerullo V; Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Viitala T; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Sarmento B; i3S - Instituto de Investigação e Inovação em Saúde, University of Porto, 4200-135, Porto, Portugal.; INEB - Instituto de Engenharia Biomédica, University of Porto, 4200-135, Porto, Portugal.; CESPU - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, 4585-116, Gandra, Portugal., Hirvonen J; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland., Santos HA; Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014, Helsinki, Finland.; Helsinki Institute of Life Science (HiLIFE), University of Helsinki, FI-00014, Helsinki, Finland. |
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| Jazyk: | angličtina |
| Zdroj: | Bioactive materials [Bioact Mater] 2021 Aug 10; Vol. 9, pp. 299-315. Date of Electronic Publication: 2021 Aug 10 (Print Publication: 2022). |
| DOI: | 10.1016/j.bioactmat.2021.08.007 |
| Abstrakt: | Oral insulin delivery could change the life of millions of diabetic patients as an effective, safe, easy-to-use, and affordable alternative to insulin injections, known by an inherently thwarted patient compliance. Here, we designed a multistage nanoparticle (NP) system capable of circumventing the biological barriers that lead to poor drug absorption and bioavailability after oral administration. The nanosystem consists of an insulin-loaded porous silicon NP encapsulated into a pH-responsive lignin matrix, and surface-functionalized with the Fc fragment of immunoglobulin G, which acts as a targeting ligand for the neonatal Fc receptor (FcRn). The developed NPs presented small size (211 ± 1 nm) and narrow size distribution. The NPs remained intact in stomach and intestinal pH conditions, releasing the drug exclusively at pH 7.4, which mimics blood circulation. This formulation showed to be highly cytocompatible, and surface plasmon resonance studies demonstrated that FcRn-targeted NPs present higher capacity to interact and being internalized by the Caco-2 cells, which express FcRn, as demonstrated by Western blot. Ultimately, in vitro permeability studies showed that Fc-functionalized NPs induced an increase in the amount of insulin that permeated across a Caco-2/HT29-MTX co-culture model, showing apparent permeability coefficients ( P Competing Interests: The authors declare no conflict of interest. (© 2021 The Authors.) |
| Databáze: | MEDLINE |
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