Dual-functional nanoengineered carrier for controlled release and enhanced intestinal translocation: Modulating lipid transporters to boost fucoxanthin anti-obesity efficacy.

Obesity disrupts intestinal transporter function, limiting oral bioavailability and efficacy of anti-obesity bioactives. To overcome this challenge, the fucoidan-bovine serum albumin-palmitic acid (FA-BSA-PA) nanoparticles co-loaded with fucoxanthin (FUC) was engineered, leveraging PA's transporter-modulating function and FA-BSA's controlled release for nutrient-inspired delivery. In high-fat diet (HFD)-induced obese mice, FA-BSA-PA-FUC elicited significantly (P < 0.05) greater anti-obesity effects than free FUC at equivalent doses, markedly suppressing weight gain, improving blood lipid profiles, and ameliorating tissue histology. Crucially, these nanoparticles enhanced FUC absorption by upregulating scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) while suppressing P-glycoprotein (P-gp). This dual-action transporter modulation boosted FUC bioaccumulation 2.56-fold in the liver and 3.85-fold in epididymal adipose tissue. Furthermore, FA-BSA-PA-FUC profoundly (P < 0.05) regulated intestinal cholesterol metabolism: it inhibited Niemann-Pick C1-like 1 (NPC1L1)-mediated absorption (reducing jejunal and colonic NPC1L1 expression by 70 % and 45 %, respectively) and activated ATP-binding cassette transporter G5/G8 (ABCG5/G8)-mediated efflux (increasing jejunal ABCG5/G8 mRNA 7.65- and 7.73-fold). Consequently, fecal cholesterol excretion increased 2.26-fold and serum cholesterol clearance improved by 23.13 % versus the obese model group. This study demonstrates that functionalized delivery vehicles simultaneously promoting oral utilization of bioactive substances and inhibiting cholesterol absorption represent an effective strategy for obesity treatment.