Zhang Xiumei, Qiu Mingfeng, Guo Pengcheng, Lian Yumei, Xu Enge, Su Jing
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Pharmaceutics. 2018 Dec 18;10(4):286. doi: 10.3390/pharmaceutics10040286.
Although glucocorticoids are highly effective in treating various types of inflammation such as skin disease, rheumatic disease, and allergic disease, their application have been seriously limited for their high incidence of side effects, particularly in long term treatment. To improve efficacy and reduce side effects, we encapsulated betamethasone phosphate (BSP) into biocompatible red blood cells (RBCs) and explored its long acting-effect. BSP was loaded into rat autologous erythrocytes by hypotonic preswelling method, and the loading amount was about 2.5 mg/mL cells. In vitro, BSP loaded RBCs (BSP-RBCs) presented similar morphology, osmotic fragility to native RBCs (NRBCs). After the loading process, the loaded cells can maintain around 70% of Na⁺/K⁺-ATPase activity of natural cells. In vivo, a series of tests including survival, pharmacokinetics, and anti-inflammatory effect were carried out to examine the long-acting effect of BSP-RBCs. The results shown that the loaded cells could circulate in plasma for over nine days, the release of BSP can last for over seven days and the anti-inflammatory effect can still be observed on day 5 after injection. Totally, BSP-loaded autologous erythrocytes seem to be a promising sustained releasing delivery system with long anti-inflammatory effect.
尽管糖皮质激素在治疗各种类型的炎症（如皮肤病、风湿性疾病和过敏性疾病）方面非常有效，但其应用因副作用发生率高而受到严重限制，尤其是在长期治疗中。为了提高疗效并减少副作用，我们将倍他米松磷酸酯（BSP）包裹在生物相容性红细胞（RBCs）中，并探索其长效作用。通过低渗预膨胀法将BSP加载到大鼠自体红细胞中，加载量约为2.5 mg/mL细胞。在体外，加载了BSP的红细胞（BSP-RBCs）呈现出与天然红细胞（NRBCs）相似的形态和渗透脆性。加载过程后，加载的细胞可以维持天然细胞约70%的Na⁺/K⁺-ATP酶活性。在体内，进行了一系列包括存活、药代动力学和抗炎作用的测试，以检查BSP-RBCs的长效作用。结果表明，加载的细胞可以在血浆中循环超过九天，BSP的释放可以持续超过七天，并且在注射后第5天仍可观察到抗炎作用。总的来说，加载了BSP的自体红细胞似乎是一种有前途的具有长效抗炎作用的缓释递送系统。
