Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Deralakatte, Mangaluru, 575018, India.
Department of Pharmaceutics, Shree Devi College of Pharmacy, Kenjar, Mangaluru, 570142, India.
AAPS PharmSciTech. 2018 Nov;19(8):3631-3649. doi: 10.1208/s12249-018-1195-9. Epub 2018 Oct 2.
The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent (t-butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. The properties of the nano-complexes such as complexation, thermal behaviour, surface morphology, molecular crystallinity, particle size, zeta potential, drug content, solubility, in vitro stability study, in vitro drug release, in vitro and in vivo antioxidant study, in vivo hepatoprotective activity and oral bioavailability/pharmacokinetic studies were investigated. Rutin nano-complexes were developed successfully via the lyophilisation method and found to be in nanometric range. Rutin nano-complexes significantly improved the solubility and in vitro drug release, and kinetic studies confirmed the diffusion-controlled release of the drug from the formulation. The nano-complex showed better antioxidant activity in vitro and exhibited well in vitro stability in different pH media. The in vivo study showed better hepatoprotective activity of the formulation compared to pure rutin at the same dose levels with improved oral bioavailability. Carbon tetrachloride (CCl)-treated animals (group II) failed to restore the normal levels of serum hepatic marker enzymes and liver antioxidant enzyme compared to the nano-complex-treated animals. The results obtained from solubility, hepatoprotective activity and oral bioavailability studies proved the better efficacy of the nano-complex compared to the pure drug.
卵磷酯（EPC），以提高其较差的吸收和生物利用度，并研究该复合物对肝保护和抗氧化活性的影响。通过溶剂蒸发、盐析和冻干法制备芦丁纳米复合物，并对复合物形成进行比较。对于选择的冻干法，在优化后选择主要溶剂 DMSO、共溶剂（叔丁醇）和芦丁：EPC 比例（1:1、1:2 和 1:3）。对纳米复合物的性质进行了研究，如复合物形成、热行为、表面形态、分子结晶度、粒径、Zeta 电位、药物含量、溶解度、体外稳定性研究、体外药物释放、体外和体内抗氧化研究、体内肝保护活性和口服生物利用度/药代动力学研究。芦丁纳米复合物通过冻干法成功开发，并发现处于纳米级范围。芦丁纳米复合物显著提高了溶解度和体外药物释放，动力学研究证实药物从制剂中以扩散控制方式释放。纳米复合物在体外显示出更好的抗氧化活性，并在不同 pH 介质中表现出良好的体外稳定性。体内研究表明，与相同剂量水平的纯芦丁相比，该制剂具有更好的肝保护活性，口服生物利用度提高。与纳米复合物处理的动物相比，四氯化碳（CCl）处理的动物（第 II 组）未能恢复血清肝标志物酶和肝抗氧化酶的正常水平。从溶解度、肝保护活性和口服生物利用度研究中获得的结果证明了纳米复合物比纯药物具有更好的疗效。
