An ex vivo investigation of the intestinal uptake and translocation of nanoparticles targeted to Peyer's patches microfold cells

Abstract

Diverse nanoparticulate systems have been engineered as vehicles towards enhancing the bioavailability of orally administrated vaccines. Substantial evidence suggests that targeting microfold cells (M cells) within Peyer's patches (PPs) is a prerequisite for vaccine-loaded nanocarriers to induce an effective antigen-specific immune response. Improved understanding of the contribution of M cells to sampling luminal nanoparticles into the underlying gut associated lymphoid tissues would accelerate the development of oral vaccine formulations. Herein, a novel clearing-based whole tissue mount/imaging technique was developed to enable the specific distribution of nanoparticles within ex vivo murine PPs to be quantitatively determined at the cellular level. This revealed that 200 nm nanoparticles modified with M cell targeting ligands (lectin Ulex europaeus agglutinin-1, UEA-1) were translocated into subepithelial domes 7.6 and 16.3 times greater than the non-targeted ones at 60 min and 120 min, respectively. This approach provides a new methodology to quantitatively investigate the transcytotic activity of M cells for particulate formulations, which may aid in the design of improved oral vaccines.

Keywords: Microfold cells; Optical tissue clearing; Oral vaccination; Particulate nanocarriers; Quantitative analyses.