Micellar Co-Delivery of Fulvestrant and Quercetin to enhance oral Bioavailability: A potential Bioenhancement strategy.

This study aimed to develop and evaluate polymeric mixed micelles for the oral delivery of Fulvestrant (FVT), with or without Quercetin (QUE), using Soluplus® and Pluronic® F127. Among the tested weight ratios, 75:25 micelles exhibited optimal properties, including average particle sizes below 200 nm, a narrow size distribution (PDI < 0.2), high drug loading (8-8.7 %), and encapsulation efficiency > 90 %. The optimized formulations (FVT-MM and FVT-QUE-MM) showed spherical morphology, stability over 15 days, and sustained FVT release without an initial burst. In vitro, these formulations preserved the antiproliferative activity of FVT against MCF-7 cells after 72 h of treatment and maintained high cytocompatibility in Caco-2 cells (>90 %). Ex vivo Franz diffusion studies with porcine intestine revealed enhanced FVT permeation for FVT-QUE-MM (∼1.8-fold vs. FVT-MM). Both formulations also inhibited MCF-7 cell adhesion to fibronectin and migration, with stronger effects observed for FVT-QUE-MM. Oral pharmacokinetic studies in rats demonstrated significantly increased relative FVT bioavailability for FVT-MM (2.85- fold) and FVT-QUE-MM (3.71-fold) compared to FVT suspension. These findings suggest that Soluplus®/Pluronic® F127 micelles, particularly those co-loaded with QUE, represent a promising strategy to improve the oral delivery and therapeutic efficacy of FVT.