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Updated: Dec 24, 2025

Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Promoting apical-to-basolateral unidirectional transport of nanoformulations by manipulating the nutrient-absorption
Lei Wu1, Yuli Bai1, Lingling Wang1
1Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
Abstract:
The epithelium is a formidable barrier to the absorption of orally delivered nano-vehicles. Here, by exploring a nutrient-absorption pathway, a self-amplified nanoplatform was developed to promote apical-to-basolateral transcytosis across the epithelium. The nanoplatform consisted of fructose-modified polyethylene glycol coated nanoparticles (Fru-PEG NPs) and a sweetener, acesulfame potassium (AceK) in combination. Compared with regular PEGylated nanoparticles, the combination exhibited a 3.9-fold increase of absorption following oral gavage in mice and an 8.8-fold increase of transepithelial transport in vitro. When encapsulated with insulin, the combination regimen elicited a stronger hypoglycemic effect, with a pharmacological bioavailability of 18.56%, which was 3.2-fold higher than that of PEG NPs. We demonstrated that a large proportion of Fru-PEG NPs underwent internalization and basolateral exocytosis via a glucose transporter type 2 (GLUT2)-dependent process, which is an important fructose assimilation pathway. Notably, co-administered AceK could prime the epithelial cells with increased apical distribution of GLUT2, thus amplifying this unidirectional transcytosis of nanoparticles. This work is the first proof-of-concept study of manipulating and amplifying a nutrient-absorption pathway to facilitate the unidirectional trans-epithelial transport of orally administered nano-delivery vehicles.
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