UNASSIGNED: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.
UNASSIGNED: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about -23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.
UNASSIGNED: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.
■HES用于稳定类黄酮纳米晶体(NC),使用木犀草素(LUT)作为模型药物。经过全面表征,冷冻干燥和储存稳定性,溶解度,肠道吸收,药代动力学,研究了优化的HES稳定的LUTNC(LUT-HESNC)的体内抗高尿酸作用。
■制备的均匀LUT-HESNC的平均粒径为191.1±16.8nm,zeta电位约为-23mV,药物包封率98.52±1.01%,载药量为49.26±0.50%。冻干的LUT-HESNC粉末表现出良好的再分散性和9个月的储存稳定性。值得注意的是,与粗药相比,LUT-HESNC表现出改善的饱和溶解度(7.49倍),增加药物溶出速率,提高Caco-2细胞摄取(2.78倍)和口服生物利用度(Fr=355.7%)。药效学研究表明,LUT-HESNCs可显著降低高尿酸血症小鼠的血尿酸水平69.93%,改善肾脏损害。
■HES是难溶性类黄酮NC的潜在稳定剂,为这些化合物的临床应用提供了有希望的策略。LUT-HESNC可能是高尿酸血症治疗的替代或补充策略。