Abstract

Aims

This study was designed to prepare chrysophanol-loaded micelles (CLM) to improve the oral bioavailability, targetability and anti-chronic renal failure (CRF) activity of chrysophanol (CH).

Methods

The preparation of CLM was achieved via thin-film dispersion technique. The in vitro release of CLM compared with free CH was measured in phosphate buffer solution (PBS) containing 0.5%w/v sodium dodecyl sulphate (pH 6.8) while the pharmacokinetic and anti-CRF activity study was also conducted in rats. Moreover, the tissue distribution of CLM was investigated in the mice.

Results

The CLM had particle size (PS) of 29.64 ± 0.71 nm, and encapsulation efficiency (EE) of 90.48 ± 1.22%w/w. The cumulative release rate of CH from the micellar system was significantly higher than that of the free CH (86%m/m vs. 15%m/m, p < 0.01). In vivo pharmacokinetic studies showed that the bioavailability of CLM after oral administration was substantially improved (about 3.4 times) compared with free drugs (p < 0.01). Also, it was observed that CLM accumulated well in the liver and brain. Moreover, in vitro renal podocytes study showed that CLM had better protection against renal podocyte damage than the free CH. In addition, CLM significantly (p < 0.01) reduced levels of blood urea nitrogen (BUN), kidney injury molecule-1 (Kim-1), and serum creatinine (SCr), which obviously improved kidney damage in rats with CRF.

Conclusions

Collectively, these findings suggest that mixed micelles may be used as a promising drug delivery system for oral bioavailability improvement and concomitantly enhance the anti-CRF activity of CH, as well as provide a basis for the clinical application of CH.

中文翻译：

---

通过混合聚合物胶束提高大黄酚的口服生物利用度和抗慢性肾功能衰竭活性

摘要

宗旨

本研究旨在制备负载大黄酚的胶束 (CLM)，以提高大黄酚 (CH) 的口服生物利用度、靶向性和抗慢性肾功能衰竭 (CRF) 活性。

方法

CLM的制备是通过薄膜分散技术实现的。在体外与自由CH相比CLM的释放在含有0.5％磷酸缓冲溶液（PBS）测量w / v的十二烷基硫酸钠（pH6.8）中，而药代动力学和抗CRF活性研究在大鼠中也进行。此外，在小鼠中研究了 CLM 的组织分布。

结果

CLM 的粒径 (PS) 为 29.64 ± 0.71 nm，封装效率 (EE) 为 90.48 ± 1.22% w/w。胶束体系中 CH 的累积释放率显着高于游离 CH（86%m/m对15%m/m，p  < 0.01）。体内药代动力学研究表明，与游离药物相比，口服后CLM的生物利用度显着提高（约3.4倍）（p  < 0.01）。此外，还观察到 CLM 在肝脏和大脑中积累良好。此外，体外肾足细胞研究表明，CLM 比游离 CH 对肾足细胞损伤具有更好的保护作用。此外，CLM显着（p < 0.01）降低血尿素氮（BUN）、肾损伤分子-1（Kim-1）和血清肌酐（SCr）水平，明显改善CRF大鼠肾损伤。

结论

总的来说，这些发现表明混合胶束可作为一种有前景的药物递送系统，用于提高口服生物利用度并同时增强 CH 的抗 CRF 活性，并为 CH 的临床应用提供基础。