Department of Hematology, Changsha Central Hospital, Changsha, 410004, Hunan, People's Republic of China.
Department of Clinical Laboratory, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 401120, People's Republic of China.
J Nanobiotechnology. 2018 Oct 5;16(1):76. doi: 10.1186/s12951-018-0402-x.
Recently, we found that berberine (BBR) exerts anti-acute myeloid leukemia activity, particularly toward high-risk and relapsed/refractory acute myeloid leukemia MV4-11 cells in vitro. However, the poor water solubility and low bioavailability observed with oral BBR administration has limited its clinical use. Therefore, we design and develop a novel oil-in-water self-nanoemulsifying system for BBR (BBR SNE) to improve oral bioavailability and enhance BBR efficacy against acute myeloid leukemia by greatly improving its solubility.
This system (size 23.50 ± 1.67 nm, zeta potential - 3.35 ± 0.03 mV) was prepared with RH40 (surfactant), 1,2-propanediol (co-surfactant), squalene (oil) and BBR using low-energy emulsification methods. The system loaded BBR successfully according to thermal gravimetric, differential scanning calorimetry, and Fourier transform infrared spectroscopy analyses. The release profile results showed that BBR SNE released BBR more slowly than BBR solution. The relative oral bioavailability of this novel system in rabbits was significantly enhanced by 3.41-fold over that of BBR. Furthermore, Caco-2 cell monolayer transport studies showed that this system could help enhance permeation and prevent efflux of BBR. Importantly, mice with BBR SNE treatment had significantly longer survival time than BBR-treated mice (P < 0.001) in an MV4-11 engrafted leukemia murine model.
These studies confirmed that BBR SNE is a promising therapy for acute myeloid leukemia.
最近，我们发现小檗碱（BBR）在体外对急性髓系白血病 MV4-11 细胞具有抗急性作用，特别是对高危和复发/难治性急性髓系白血病。然而，口服 BBR 给药时观察到的低水溶性和生物利用度较差限制了其临床应用。因此，我们设计并开发了一种新型的 BBR 油包水自微乳给药系统（BBR SNE），以通过大大提高其溶解度来改善口服生物利用度并增强 BBR 对急性髓系白血病的疗效。
该系统（粒径 23.50±1.67nm，zeta 电位-3.35±0.03mV）是使用 RH40（表面活性剂）、1,2-丙二醇（助表面活性剂）、角鲨烯（油）和 BBR 通过低能量乳化方法制备的。热重分析、差示扫描量热法和傅里叶变换红外光谱分析表明，该系统成功加载了 BBR。释放曲线结果表明，BBR SNE 比 BBR 溶液释放 BBR 更慢。与 BBR 溶液相比，该新型系统在兔体内的相对口服生物利用度显著提高了 3.41 倍。此外，Caco-2 细胞单层转运研究表明，该系统可以帮助增强 BBR 的渗透并防止其外排。重要的是，在 MV4-11 植入白血病小鼠模型中，用 BBR SNE 治疗的小鼠的存活时间明显长于用 BBR 治疗的小鼠（P<0.001）。
这些研究证实 BBR SNE 是一种有前途的急性髓系白血病治疗方法。
