Background: Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells. However, the poor solubility and a short half-life of ZgI limit its bioavailability and efficacy. The D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) has been widely used to increase the solubility, improve the encapsulation rate, and extend the half-life of drugs.
Methods: Here, we formulated the TPGS-modified long-circulating liposomes loading ZgI with a sustained drug release and enhanced therapy for myelosuppression. ZgI-TPGS-liposomes were manufactured using a thin-film hydration technique, followed by characterizations of physicochemical properties, including the particle size, zeta potential, TEM, SEM, FTIR, XRD, stability, drug loading (DL), encapsulation efficiency (EE). The in vitro and in vivo delivery efficiency were further evaluated by cellular uptake, in vitro drug release and in vivo pharmacokinetics. Finally, therapeutic effect on myelosuppression was investigated.
Results: The ZgI-TPGS-liposomes had an particle size of 97.89 ± 1.42 nm and ZP of − 28.65 ± 0.16 mV. It exhibited DL of 9.06 ± 0.76% and EE of 92.34 ± 3.83%, along with excellent storage stability, cellular uptake and sustained drug release to free ZgI and liposomes without TPGS. Additionally, the TPGS modified liposomes significantly enhanced the therapeutic effect of ZgI on CTX induced myelosuppression, which can be confirmed in the apoptosis inhibition and cell viability promotion of CTX injured HSPC-1 cells. Also, the mice in vivo pharmacodynamics demonstrated that TPGS liposomes promoted ZgI increasing the numbers of leucocytes and neutrophils in myelosuppression mice induced by CTX.
Conclusion: Our research suggest that TPGS-modified long-circulating liposomes loading ziyuglycoside I has potential application in myelosuppression therapy.



中文翻译：

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TPGS 修饰的长循环脂质体负载紫玉甙 I 增强骨髓抑制治疗

背景：紫玉甙 I ( ZgI ) 是一种从中药地榆中分离的活性成分，已被证明可增加白细胞并保护造血干细胞。然而，ZgI 的溶解度差和半衰期短限制了其生物利用度和功效。D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）已被广泛用于增加溶解度、提高包封率、延长药物半衰期。
方法：在这里，我们配制了负载 ZgI 的 TPGS 修饰的长循环脂质体，具有持续的药物释放和增强的骨髓抑制治疗。ZgI-TPGS-脂质体采用薄膜水合技术制备，随后对其物理化学性质进行表征，包括粒径、zeta 电位、TEM、SEM、FTIR、XRD、稳定性、载药量 (DL)、包封率 (EE) ）。通过细胞摄取、体外药物释放和体内药代动力学进一步评估体外和体内递送效率。最后，研究了对骨髓抑制的治疗效果。
结果：ZgI-TPGS-脂质体的粒径为 97.89 ± 1.42 nm，ZP 为 - 28.65 ± 0.16 mV。它表现出 9.06 ± 0.76% 的 DL 和 92.34 ± 3.83% 的 EE，以及出色的储存稳定性、细胞摄取和持续药物释放，以游离 ZgI 和不含 TPGS 的脂质体。此外，TPGS修饰的脂质体显着增强了ZgI对CTX诱导的骨髓抑制的治疗作用，这可以在CTX损伤的HSPC-1细胞的凋亡抑制和细胞活力促进中得到证实。此外，小鼠体内药效学表明，TPGS 脂质体促进 ZgI 增加由 CTX 诱导的骨髓抑制小鼠的白细胞和中性粒细胞数量。
结论：我们的研究表明，TPGS修饰的长循环脂质体负载紫玉甙I在骨髓抑制治疗中具有潜在的应用价值。