Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China; Beijing Key Laboratory of Bio-characteristic Profiling for Evaluation of Clinical Rational Drug Use, Beijing, 100038, China.
Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China; Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, China.
Biomed Pharmacother. 2020 Jul;127:110140. doi: 10.1016/j.biopha.2020.110140. Epub 2020 May 5.
Berberine (BBR) is a potential novel agent to treat diabetes, but its oral bioavailability is restricted by the poor solubility, which greatly limits its clinical application. Here, a new drug delivery system of BBR-MgAl monolayer hydrotalcite (BBR/MLDH) was prepared to increase the solubility and bioavailability of BBR. The results showed that BBR/MLDH presented as a uniform hexagonal plate-like particle with a loading capacity of 28.61 %, a diameter of ∼70 nm and a thickness of ∼1.5 nm. The solubility and dissolution of BBR increased when loading onto MLDH. Compared with BBR, pharmacokinetics of BBR/MLDH in rats showed significant enhancement (P < 0.01) in area under the curve (AUC) and the peak plasma concentration (C), suggesting the bioavailability of BBR was improved. Furthermore, BBR/MLDH showed more potent effects in reducing fasting blood glucose, ameliorating glucose tolerance and insulin resistance comparing to the equivalent dose of BBR. In a word, the solubility, oral bioavailability and hypoglycemic effect of BBR could be improved by loading onto MLDH.
小檗碱（BBR）是一种有潜力的治疗糖尿病的新型药物，但由于其溶解度较差，口服生物利用度受到限制，这极大地限制了其临床应用。本文制备了小檗碱-镁铝层状双氢氧化物（BBR/MLDH）新的给药系统，以提高 BBR 的溶解度和生物利用度。结果表明，BBR/MLDH 呈均匀的六方片状颗粒，载药量为 28.61%，粒径约为 70nm，厚度约为 1.5nm。当负载到 MLDH 上时，BBR 的溶解度和溶解速度增加。与 BBR 相比，BBR/MLDH 在大鼠体内的药代动力学表现出明显的增强（P<0.01），表现在曲线下面积（AUC）和峰血浆浓度（C）增加，表明 BBR 的生物利用度得到了提高。此外，与等剂量的 BBR 相比，BBR/MLDH 降低空腹血糖、改善葡萄糖耐量和胰岛素抵抗的作用更强。总之，通过负载到 MLDH 上可以提高 BBR 的溶解度、口服生物利用度和降血糖作用。
