# Brucea javanica-Derived Natural Lipid Droplets: Selective Oral Lymph Targeting and Endocytic Transport Mechanisms

## TL;DR

This study shows that natural lipid droplets from Brucea javanica can improve drug delivery by targeting the lymphatic system and reducing degradation.

## Contribution

The study introduces a novel 'drug-in-carrier' delivery platform using plant-derived lipid droplets with high lymphatic targeting efficiency.

## Key findings

- BJLDs showed 80% fatty acid release within 4 hours following first-order kinetics.
- Caveolin-dependent endocytosis was the main uptake route in Caco-2 cells with 2.3-fold higher drug accumulation.
- Lymphatic transport rate reached 89.73% in a rat model with extended drug retention confirmed via LC-MS/MS.

## Abstract

Background: Brucea javanica oil (BJO) suffers from poor oral bioavailability due to oxidative degradation and hepatic first-pass effect. Methods: Here, we report a one-step, solvent-free isolation of endogenous Brucea javanica lipid droplets (BJLDs) that function as a “drug-in-carrier” delivery platform. Results: BJLDs exhibited a uniform size distribution and superior oxidative stability. In vitro digestion showed 80% long-chain fatty acids released within 4 h following first-order kinetics. Caco-2 transport studies revealed caveolin-dependent endocytosis as the dominant uptake route and a 2.3-fold increase in rhodamine 123 accumulation versus free drug, indicating potent P-gp inhibition. A cycloheximide-blocked rat model quantified the intestinal lymphatic transport rate at 89.73%. Plasma t1/2 and MRT of linoleic acid were 8.44 ± 3.16 h and 11.45 ± 2.72 h, respectively. LC-MS/MS confirmed retention of brusatol and bruceine inside BJLDs. Conclusions: This study provides direct evidence that micron-sized lipid droplets derived from plants can achieve >80% lymphatic targeting after oral administration, offering a green and scalable alternative to conventional BJO formulations.