Chylomicron-Mimicking Supramolecular Nanoemulsion for Oral Luteolin Delivery against Hyperuricemia

Hyperuricemia, a prevalent metabolic disorder, severely impacts life quality. Luteolin (LUT), a natural flavonoid compound, demonstrates potential anti-hyperuricemic effects along with a high safety profile. However, its clinical application is greatly limited by poor oral bioavailability, mainly due to low permeability and inadequate gastrointestinal stability. To address this, we developed a chylomicron-mimicking supramolecular nanoemulsion (LUT-CMSN) composed of soybean oil and a supramolecular aggregate formed between LUT and Kolliphor® HS 15 (HS 15). LUT-CMSN exhibited a near-spherical morphology with an average particle size of approximately 14.2 nm. With CMSN encapsulation, LUT exhibited notably improved permeability and stability in the gastrointestinal tract. After oral administration, LUT-CMSN could be absorbed by lymphatic transport into blood circulation, consequently achieving 4.63-fold higher Cmax and 2.59-fold greater AUC(0–t) compared with free LUT. Additionally, LUT-CMSN showed markedly enhanced distribution in the liver and kidney relative to free LUT. In the acute and chronic hyperuricemia animal model, LUT-CMSN effectively reduced serum uric acid levels through inhibition of xanthine oxidase (XOD) activity and observably alleviated the renal injury induced by hyperuricemia. Taken together, LUT-CMSN represents a promising oral delivery platform for enhancing the bioavailability of LUT and a potential therapeutic strategy for the treatment of hyperuricemia.