School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
Drug Deliv. 2020 Dec;27(1):283-291. doi: 10.1080/10717544.2020.1716880.
Discovery of novel pharmacological effects of berberine hydrochloride (BH) has made its clinical application valuable. However, further development and applications of BH are hampered by its short half-life and the side effects associated with its intravenous (iv) injection. To improve the hypolipidemia efficacy and reduce side effects, we encapsulated BH into biocompatible red blood cells (RBCs) to explore its sustained-release effect by hypotonic pre-swelling method. From evaluation, BH loaded RBCs (BH-RBCs) presented similar morphology and osmotic fragility to native RBCs (NRBCs). After the loading process, the BH-RBCs maintained around 69% of Na/K-ATPase activity of NRBCs and phosphatidylserine externalization value of BH-RBCs was about 26.1 ± 2.9%. The survival test showed that the loaded cells could circulate in plasma for over 9 d. For evaluation, a series of tests including pharmacokinetics study and hypolipidemic effect were carried out to examine the long-acting effect of BH-RBCs. The results showed that the release of BH in the loaded cells could last for about 5 d and the hypolipidemic effect can still be observed on 5 d after injection. BH-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long hypolipidemic effect.
盐酸小檗碱（BH）新的药理作用的发现使其具有临床应用价值。然而，由于其半衰期短以及静脉注射（iv）相关的副作用，其进一步的开发和应用受到了阻碍。为了提高降脂疗效和降低副作用，我们采用低渗预膨胀法将 BH 包封到生物相容性的红细胞（RBC）中，以探索其持续释放效果。从评价结果来看，BH 负载 RBC（BH-RBC）的形态和渗透脆性与天然 RBC（NRBC）相似。在加载过程之后，BH-RBC 维持了 NRBC 的 Na/K-ATPase 活性的约 69%，并且 BH-RBC 的磷脂酰丝氨酸外翻值约为 26.1±2.9%。存活试验表明，负载的细胞可以在血浆中循环超过 9 天。从评价结果来看，进行了一系列的测试，包括药代动力学研究和降脂效果，以检查 BH-RBC 的长效作用。结果表明，负载细胞中的 BH 释放可以持续约 5 天，并且在注射后 5 天仍可以观察到降脂效果。载有 BH 的自体红细胞似乎是一种具有长期降脂作用的有前途的持续释放递送系统。
