Hydroxypropyl-β-cyclodextrin as a co-delivery vehicle for synergistically enhancing fucoxanthin oral bioavailability through dual regulation of SR-B1 and ABCB1 transporters

Hydroxypropyl-β-cyclodextrin (HPβCD) serves as an effective carrier for enhancing the delivery of poorly soluble actives. In this work, an HPβCD-based delivery system encapsulating the marine carotenoid fucoxanthin (FUCO) and the transporter-regulating isoquercitrin (IQ) was prepared via high-pressure homogenization (HPH). The Caco-2 monolayer model demonstrated that IQ significantly enhanced FUCO transport across the intestinal barrier. This effect arose from IQ's synergistic action: promoting scavenger receptor class B type 1 (SR-B1)-dependent endocytic uptake while inhibiting ATP-binding cassette transporter B1 (ABCB1)-mediated efflux. At the optimal IQ/FUCO molar ratio (1: 2), SR-B1 expression increased 1.3-fold, ABCB1 expression decreased by 70.7%, and FUCO transmembrane transport rose 14.5-fold. Under the optimized conditions, HPβCD achieved an 88.7% encapsulation efficiency of FUCO. Fourier transform infrared spectroscopy (FTIR), electron microscopy observations, and X-ray diffraction (XRD) confirmed the encapsulation of FUCO and IQ within HPβCD's hydrophobic cavity. In vivo studies demonstrated that HPβCD-based delivery of IQ dramatically enhanced FUCO's oral bioavailability, elevating hepatic exposure of FUCO and its metabolites by 3.28-fold. Simultaneously, a 1.5-fold increase in intestinal SR-B1 expression and a 20% inhibition of ABCB1 expression were also observed. This work validates a "carrier encapsulation-transporter modulation" dual strategy, combining HPβCD encapsulation with IQ-mediated regulation of key transporters (SR-B1/ABCB1), providing a novel approach for the efficient development of marine-derived nutraceuticals.

Fucoxanthin; High-pressure homogenization; Hydroxypropyl-β-cyclodextrin; Intestinal absorption; Isoquercitrin; Transporters.