Microfluidic Nanoassembly of Bioengineered Chitosan-Modified FcRn-Targeted Porous Silicon Nanoparticles @ Hypromellose Acetate Succinate for Oral Delivery of AntiDiabetic Peptides

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Abstrakti

Microfluidics technology is emerging as a promising strategy to improve the oral delivery of proteins and peptides. Herein, a multistage drug delivery system is proposed as a step forward in the development of non-invasive therapies. Undecylenic acid modified thermally hydrocarbonized porous silicon (UnPSi) nanoparticles (NPs) were functionalized with the Fc fragment of immunoglobulin G for targeting purposes. Glucagon like peptide-1 (GLP-1) was loaded into the NPs as a model anti-diabetic drug. Fc-UnPSi NPs were coated with mucoadhesive chitosan, and ultimately entrapped into a polymeric matrix with pH-responsive properties by microfluidic nanoprecipitation. The final formulation showed a controlled and narrow size distribution. The pH-responsive matrix remained intact in acidic conditions, dissolving only in intestinal pH, resulting in a sustained release of the payload. The NPs presented high cytocompatibility, and increased levels of interaction with intestinal cells when functionalized with the Fc fragment, which was supported by the validation of the Fc fragment integrity after conjugation to the NPs. Finally, the Fc-conjugated NPs showed augmented GLP-1 permeability in an intestinal in vitro model. These results highlight the potential of microfluidics as an advanced technique for the preparation of multistage platforms for oral administration. Moreover, this study provides new insights on the potential of the FcRn transcytotic capacity for the development of targeted therapies.
Alkuperäiskielienglanti
LehtiACS Applied Materials & Interfaces
Vuosikerta10
Numero51
Sivut44354–44367
Sivumäärä14
ISSN1944-8244
DOI - pysyväislinkit
TilaJulkaistu - 7 joulukuuta 2018
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 317 Farmasia

Siteeraa tätä