TY - JOUR
T1 - Neonatal Fc receptor-targeted lignin-encapsulated porous silicon nanoparticles for enhanced cellular interactions and insulin permeation across the intestinal epithelium
AU - Martins, João P.
AU - Figueiredo, Patrícia
AU - Wang, Shiqi
AU - Espo, Erika
AU - Celi, Elena
AU - Martins, Beatriz
AU - Kemell, Marianna
AU - Moslova, Karina
AU - Mäkilä, Ermei
AU - Salonen, Jarno
AU - Kostiainen, Mauri A.
AU - Celia, Christian
AU - Cerullo, Vincenzo
AU - Viitala, Tapani
AU - Sarmento, Bruno
AU - Hirvonen, Jouni
AU - Santos, Hélder A.
N1 - Funding Information:
Dr. Shiqi Wang acknowledges financial support from Academy of Finland (decision no. 331106 ). Prof. Hélder A. Santos acknowledges financial support from the HiLIFE Research Funds, the Sigrid Jusélius Foundation (decision no. 4704580 ) and the Academy of Finland (grant no. 317042 and 331151 ). The authors acknowledge the following core facilities funded by Biocenter Finland: Electron Microscopy Unity of the University of Helsinki, Finland for providing the facilities for TEM imaging. The authors acknowledge the use of ALD center Finland research infrastructure for EDX measurements. The authors acknowledge Tomás Bauleth-Ramos for technical support with the cell viability assays.
Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - 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 (Papp) of 2.37 × 10−6 cm/s, over the 1.66 × 10−6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.
AB - 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 (Papp) of 2.37 × 10−6 cm/s, over the 1.66 × 10−6 cm/s observed for their non-functionalized counterparts. Overall, these results demonstrate the potential of these NPs for oral delivery of anti-diabetic drugs.
KW - FcRn
KW - Insulin
KW - Lignin
KW - Nanoparticles
KW - Oral drug delivery
KW - Porous silicon
UR - http://www.scopus.com/inward/record.url?scp=85112562867&partnerID=8YFLogxK
U2 - 10.1016/j.bioactmat.2021.08.007
DO - 10.1016/j.bioactmat.2021.08.007
M3 - Article
C2 - 34820572
AN - SCOPUS:85112562867
SN - 2452-199X
VL - 9
SP - 299
EP - 315
JO - Bioactive materials
JF - Bioactive materials
ER -