Preparation of etoposide liposomes for enhancing antitumor efficacy on small cell lung cancer and reducing hematotoxicity of drugs,European Journal of Pharmaceutics and Biopharmaceutics

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Preparation of etoposide liposomes for enhancing antitumor efficacy on small cell lung cancer and reducing hematotoxicity of drugs
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2024-03-06 , DOI: 10.1016/j.ejpb.2024.114239
Ruixue Huang ₁ , Huali Chen ₁ , Damao Pi ₂ , Xuemei He ₃ , Chao Yu ₄ , Chaoqun Yu ₁

Affiliation

Etoposide (VP16) is commonly used in the treatment of small cell lung cancer (SCLC) in clinical practice. However, severe adverse reactions such as bone marrow suppression toxicity limit its clinical application. Although several studies on VP16 liposomes were reported, no significant improvement in bone marrow suppression toxicity has been found, and there was a lack of validation of animal models for in vivo antitumor effects. Therefore, we attempted to develop a PEGylated liposomal formulation that effectively encapsulated VP16 (VP16-LPs) and evaluated its therapeutic effect and toxicity at the cellular level and in animal models. First, we optimized the preparation process of VP16-LPs using an orthogonal experimental design and further prepared them into freeze-dried powder to improve storage stability of the product. Results showed that VP16-LPs freeze-dried powder exhibited good dispersibility and stability after redispersion. In addition, compared to marketed VP16 injection, VP16-LPs exhibited sustained drug release characteristics. At the cellular level, VP16-LPs enhanced the cellular uptake of drugs and exhibited strong cytotoxic activity. In animal models, VP16-LPs could target and aggregate in tumors and exhibit a higher anti-tumor effect than VP16-injection after intravenous injection. Most importantly, hematological analysis results showed that VP16-LPs significantly alleviated the bone marrow suppression toxicity of drug. In summary, our study confirmed that PEGylated liposomes could enhance therapeutic efficacy and reduce toxicity of VP16, which demonstrated that VP16-LPs had enormous clinical application potential.

中文翻译：

增强小细胞肺癌抗肿瘤疗效并降低药物血液毒性的依托泊苷脂质体的制备

依托泊苷（VP16）在临床实践中常用于治疗小细胞肺癌（SCLC）。但骨髓抑制毒性等严重不良反应限制了其临床应用。尽管已有多项关于VP16脂质体的研究报道，但未发现骨髓抑制毒性的显着改善，并且缺乏动物模型的体内抗肿瘤作用验证。因此，我们试图开发一种有效封装VP16（VP16-LPs）的聚乙二醇化脂质体制剂，并在细胞水平和动物模型中评估其治疗效果和毒性。首先，我们利用正交实验设计优化了VP16-LPs的制备工艺，并进一步将其制备成冻干粉，以提高产品的储存稳定性。结果表明，VP16-LPs冻干粉再分散后表现出良好的分散性和稳定性。此外，与市售的VP16注射液相比，VP16-LPs表现出持续的药物释放特性。在细胞水平上，VP16-LPs增强了细胞对药物的摄取并表现出很强的细胞毒活性。在动物模型中，VP16-LPs可以在肿瘤中靶向聚集，静脉注射后表现出比VP16注射液更高的抗肿瘤作用。最重要的是，血液学分析结果表明VP16-LPs显着减轻了药物的骨髓抑制毒性。综上所述，我们的研究证实聚乙二醇化脂质体可以增强VP16的治疗效果并降低VP16的毒性，这表明VP16-LPs具有巨大的临床应用潜力。

更新日期：2024-03-06

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