PDF(Pubmed)
Abstract：
UNASSIGNED: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.
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.
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.
摘要：
■尽管类黄酮化合物表现出多种药理活性，它们的临床应用受到低口服生物利用度的限制，因为它们的溶解性差。纳米晶体（NC）代表了提高类黄酮口服生物利用度的极好策略。羟乙基淀粉(HES),一种用作血浆扩张器的生物材料化合物，可能是制备类黄酮NCs的理想稳定剂材料。
■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。
■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。
