Solubilization of Paclitaxel with Natural Compound Rubusoside toward Improving Oral Bioavailability in a Rodent Model

Area of Science:

• Pharmacology
• Materials Science
• Nanotechnology

Background:

• Paclitaxel exhibits poor water solubility and permeability, limiting oral drug delivery.
• Current paclitaxel formulations require intravenous administration due to low oral absorption.
• Efflux pump substrates like paclitaxel face challenges in achieving therapeutic bioavailability via oral routes.

Purpose of the Study:

• To evaluate rubusoside, a natural compound, for enhancing paclitaxel's oral bioavailability.
• To develop paclitaxel nano-micelles using rubusoside for improved drug delivery.
• To compare the oral bioavailability of paclitaxel nano-micelles with conventional Taxol formulation.

Main Methods:

• Paclitaxel was formulated into nano-micelles using rubusoside in an aqueous solution.
• Particle size of the nano-micelles was measured using dynamic light scattering.
• Oral and intravenous administration of paclitaxel nano-micelles and Taxol in Sprague Dawley rats to determine bioavailability.

Main Results:

• Rubusoside-formed paclitaxel nano-micelles achieved a supersaturated concentration of 6 mg/mL.
• The mean particle size of the nano-micelles was 4.7 ± 0.7 nm.
• Relative oral bioavailability increased by 88%, with maximum blood concentration 1.5-fold higher compared to Taxol.

Conclusions:

• Rubusoside effectively solubilizes paclitaxel into nano-micelles, improving its oral bioavailability.
• Despite improvements, absolute oral bioavailability remains low, suggesting further strategies are necessary.
• Inhibiting efflux pumps and/or first-pass metabolism could enhance oral paclitaxel delivery.