Abstract
The aim of this study was to probe whether the transferrin (Tf) transport pathway can be exploited for intestinal delivery of nanoparticles. Tf was adsorbed on 100 nm model polystyrene nanoparticles (NP), followed by size characterisation of these systems. Cell uptake of Tf and Tf-adsorbed NP was investigated in intestinal epithelial Caco-2 cells cultured on multi-well plates and as differentiated polarised monolayers. Tf-NP demonstrated a remarkably higher cell uptake compared to unmodified NP in both non-polarised (5-fold) and polarised cell monolayers (16-fold difference). Application of soluble Tf significantly attenuated the uptake of Tf-NP. Notably, Tf-NP displayed remarkably higher rate (23-fold) of epithelial transport across Caco-2 monolayers compared to unmodified NP. This study therefore strongly suggests that the Tf transport pathway should be considered as a candidate biological transport route for orally-administered nanomedicines and drugs with poor oral bioavailability.
Highlights
The oral drug administration route offers the ultimate patient convenience, preference and adherence to drug therapy
As a rapidly expanding class of drugs, biologics are presently predominantly given by injection
We show here that transferrin receptor (TfR) targeting of NP significantly improves their uptake into intestinal epithelial cells (Caco-2), as well as translocation across cell monolayers serving as an in vitro intestinal model
Summary
The oral drug administration route offers the ultimate patient convenience, preference and adherence to drug therapy. With a few exceptions, oral administration is currently an option only for small drug molecules that show acceptable intestinal absorption. Drug delivery strategies in this area mostly utilise absorption or permeation enhancers and focus on smaller biologics, such as glucagon-like peptide 1 (GLP-1) analogues [1]. Safety concerns, including those related to many surfactants [2], have hindered the clinical translation of these approaches. Recent progress in this area seeks to utilise advances in materials, engineering and electronics, leading to swallowable “devices”, such as mucoadhesive patches [3] and the microneedle “robotic pill” [4]
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