Lymph-Targeted Delivery of CUR-NLCs Enhances Oral Bioavailability: Evidence from a Double-Catheterized Rat Model

Area of Science:

• Pharmacology and Drug Delivery
• Nanotechnology in Medicine
• Gastrointestinal Absorption Mechanisms

Background:

• Curcumin (CUR) exhibits poor oral bioavailability due to low solubility and extensive first-pass metabolism.
• CUR-loaded nanostructured lipid carriers (CUR-NLCs) show potential for improved oral absorption, but lymphatic transport mechanisms require direct evidence.
• Existing understanding of CUR-NLCs' oral absorption is largely based on indirect evidence.

Purpose of the Study:

• To directly investigate the intestinal lymphatic transport mechanism of CUR-NLCs.
• To evaluate the pharmacokinetic benefits of CUR-NLCs compared to free CUR after oral administration.
• To provide direct evidence for enhanced oral bioavailability mediated by lymphatic transport.

Main Methods:

• CUR-NLCs were synthesized and characterized for physicochemical properties (size, zeta potential, EE, DL, stability, release).
• A rat model with a mesenteric lymph duct-jugular vein shunt was used to collect lymph and assess drug transport.
• Transmission electron microscopy (TEM) was employed to visualize cellular uptake and chylomicron formation.

Main Results:

• CUR-NLCs demonstrated favorable physicochemical properties (117.28 nm size, 99.99% EE, 1.73% DL) with sustained release.
• Oral administration of CUR-NLCs resulted in a 5.13-fold increase in relative bioavailability and a 5.25-fold increase in Cmax compared to free CUR.
• Curcumin was exclusively detected in lymph following CUR-NLC administration, confirming lymphatic transport, supported by TEM findings of chylomicrons.

Conclusions:

• CUR-NLCs effectively enhance oral bioavailability through direct intestinal lymphatic absorption.
• This study provides direct evidence for the lymphatic transport pathway of CUR-NLCs.
• CUR-NLCs represent a viable strategy for improving the oral delivery of hydrophobic drugs with poor solubility.