# Membrane-Mediated Nanoassembly of Lysozyme–Tannic Acid for Crystallization-Suppressed Nobiletin Delivery: Enhanced Cellular Uptake and Mucus Penetration

## TL;DR

Researchers developed a nanoparticle system to improve the absorption and delivery of a poorly soluble drug called nobiletin, enhancing its cellular uptake and mucus penetration.

## Contribution

A novel lysozyme–tannic acid nanoparticle system that prevents drug crystallization and enhances mucosal permeation of nobiletin.

## Key findings

- LT-NOB nanoparticles achieved 89.5% encapsulation efficiency and 47.25% drug loading.
- LT-NOB improved mucosal permeation by 75% in Caco-2 models and 50% in co-culture models.
- Cellular uptake occurred via macropinocytosis with lysosomal escape and endoplasmic reticulum targeting.

## Abstract

To enhance the bioavailability of hydrophobic nobiletin (NOB), this study constructed nanoparticles (LT-NOB) via self-assembly of lysozyme and tannic acid (TA). The multivalent weak interaction network between TA and lysozyme effectively encapsulated amorphous NOB, inhibiting crystallization. The optimized LT-NOB exhibited a size of 212 nm, high encapsulation efficiency (89.5%), and drug loading (47.25%). Cellular uptake was significantly improved, primarily through macropinocytosis, followed by lysosomal escape and endoplasmic reticulum targeting. In Caco-2 and co-culture models, LT-NOB enhanced mucosal permeation by 75% and 50%, respectively, compared to free NOB. This work elucidates a robust strategy for stabilizing amorphous drugs and promoting their intestinal absorption, providing a foundation for advanced nanodrug delivery.