State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10 Tuanbo New Town West District, Poyang Lake Road, Jinghai District, 301617, Tianjin, China.
Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin, 301617, China.
Drug Deliv Transl Res. 2022 Dec;12(12):3017-3028. doi: 10.1007/s13346-022-01167-w. Epub 2022 Apr 27.
Baicalin (BA)-berberine (BBR) have been proposed as the couple in the prevention and treatment of numerous diseases due to their multiple functional attributes. However, with regard to certain factors involving unsatisfactory aqueous solubility and low bioavailability associated with its clinical application, there is need for continuous researches by scientist. In this study, after successfully preparing BA-BBR complex, BA-BBR complex nanocrystals were obtained through high-pressure homogenization and evaluated (in vitro and in vivo). The particle size, distribution, morphology, and crystalline properties for the optimal BA-BBR complex nanocrystals were characterized by the use of scanning electron microscope, dynamic light scattering, powder X-ray diffraction, and differential scanning calorimetry. The particle size and poly-dispersity index of BA-BBR complex nanocrystals were 318.40 ± 3.32 nm and 0.26 ± 0.03, respectively. In addition, evaluation of the in vitro dissolution extent indicated that BA and BBR in BA-BBR complex nanocrystals were 3.30- and 2.35-fold than BA-BBR complex. Subsequently, single-pass intestinal perfusion combined with microdialysis test and oral pharmacokinetics in SD rats was employed to evaluate the in vivo absorption improvement of BA-BBR complex nanocrystals. The pharmacokinetics results exhibited that the area under curve of BA and BBR in the BA-BBR complex nanocrystals group were 622.65 ± 456.95 h·ng/ml and 167.28 ± 78.87 h·ng/ml, respectively, which were separately 7.49- and 2.64-fold than the complex coarse suspension. In conclusion, the above results indicate that the developed and optimized BA-BBR complex nanocrystals could improve the dissolution rate and extent and oral bioavailability, as well as facilitate the co-absorption of the drug prescriptions BA and BBR.
黄芩苷（BA）-小檗碱（BBR）由于其多种功能特性，已被提议作为预防和治疗许多疾病的组合。然而，由于其临床应用相关的水溶解度不理想和生物利用度低等某些因素，仍需要科学家们进行持续的研究。在本研究中，成功制备 BA-BBR 复合物后，通过高压匀质法获得了 BA-BBR 复合纳米晶体，并进行了评价（体外和体内）。使用扫描电子显微镜、动态光散射、粉末 X 射线衍射和差示扫描量热法对最佳 BA-BBR 复合纳米晶体的粒径、分布、形态和结晶性质进行了表征。BA-BBR 复合纳米晶体的粒径和多分散指数分别为 318.40 ± 3.32nm 和 0.26 ± 0.03。此外，体外溶解程度的评估表明，BA-BBR 复合纳米晶体中的 BA 和 BBR 分别是 BA-BBR 复合的 3.30 倍和 2.35 倍。随后，采用单次肠灌流结合微透析试验和 SD 大鼠口服药代动力学评价 BA-BBR 复合纳米晶体的体内吸收改善情况。药代动力学结果表明，BA-BBR 复合纳米晶体组中 BA 和 BBR 的曲线下面积分别为 622.65 ± 456.95 h·ng/ml 和 167.28 ± 78.87 h·ng/ml，分别是复合物粗混悬液的 7.49 倍和 2.64 倍。综上所述，上述结果表明，所开发和优化的 BA-BBR 复合纳米晶体能够提高药物的溶解速率和程度以及口服生物利用度，并促进药物 BA 和 BBR 的共同吸收。
