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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Research Article

联合递送紫杉醇和双氢青蒿素的混合纳米粒子显示协同抗癌治疗

卷 24, 期 12, 2024

发表于: 06 February, 2024

页: [1250 - 1261] 页: 12

弟呕挨: 10.2174/0115680096283208231229103822

价格: $65

摘要

目标：抗癌治疗需要提供有效和安全的患者药物。这项研究有助于开发和应用纳米颗粒(NPs)用于癌症治疗。 背景：紫杉醇(PTX)溶解度差，由于配方辅料的过敏性副作用，限制了其治疗效果。为了克服这一问题，PTX与青蒿素衍生物偶联并装载到NP给药系统中，以增强其作用，同时解决其低溶解度问题。 目的：本研究制备并表征了一种含有双氢青蒿素(DHA)和PTX的杂化PLGA -卵磷脂NP，用于协同抗癌。冻干研究提高了NP药物制剂的稳定性。 方法：采用单步溶剂蒸发法制备了PTX和DHA双负载PLGA和卵磷脂基NPs。对NP悬浮液进行冻干，并研究了冷冻保护剂的种类和配比。对NPs和冻干饼(Lyo-NPs)的理化性质进行了表征。研究了Lyo-NPs在2-8℃和室温条件下的稳定性。采用体外细胞毒性实验和体内模型分析了联合用药、NP悬浮液和冻干粉的抗癌作用。 结果：制备了最佳PTX-DHA负载plga -卵磷脂- np (200 nm, PDI: 0.248 μ} 0.003, Zeta电位:-33.60 μ} 3.39 mV)。选择甘露醇进行冻干。Lyo-NPs提高了NPs的稳定性(1年)，其中NPs的物理化学性质保持不变(RDI接近1.0)。PTX与DHA联合体外细胞毒性试验显示出协同抗癌作用(CI <1.0)。Lyo-NPs对体内肿瘤生长的抑制作用呈剂量依赖性。虽然游离药物混合物在体内显示出高毒性(7.5 mg PTX-15 mg DHA/kg)，但Lyo-NPs在血液学和生化参数方面与对照组相比没有统计学差异。 结论：双药负载的杂化PLGA -卵磷脂NP是一种潜在的系统，可以在减少严重副作用的同时增强抗肿瘤疗效，其中冻干是增加稳定性的关键过程。

关键词: 紫杉醇，协同治疗，杂交纳米粒子，抗癌治疗，冻干，稳定性，青蒿素衍生物。

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