Department of Pharmaceutical Industry, Faculty of Pharmaceutical Technology, Hanoi University of Pharmacy, Hanoi, Vietnam.
Faculty of Pharmacy, HaiPhong University of Medicine and Pharmacy, Hai-Phong, VietNam.
Curr Cancer Drug Targets. 2024;24(12):1250-1261. doi: 10.2174/0115680096283208231229103822.
Anticancer treatment is required to provide effective and safe patient medicines. This research aided in developing and applying nanoparticles (NPs) for cancer treatment.
The poor solubility of paclitaxel (PTX) restricts its therapeutic efficacy because of allergic side effects caused by formulation excipients. To overcome this, PTX was coupled with artemisinin derivatives and loaded into an NP drug delivery system to enhance its effects while addressing its low solubility.
This study prepared and characterized a hybrid PLGA-lecithin NP containing dihydroartemisinin (DHA) and PTX for synergic anticancer therapy. A lyophilization study improved the stability of the NP drug formulations.
Dual PTX- and DHA-loaded PLGA- and lecithin-based NPs were prepared using a single-step solvent evaporation method. The NP suspensions were lyophilized, and the types and ratios of cryoprotectants were investigated. The physicochemical properties of NPs and lyophilized cakes (Lyo-NPs) were characterized. The stability of the Lyo-NPs was investigated at 2-8°C and room conditions. The anticancer effects of the drug combination, NP suspension, and lyophilized powder were analyzed using an in vitro cytotoxicity assay and an model.
The optimal PTX-DHA loaded PLGA-lecithin-NP was formulated (200 nm, PDI: 0.248 ± 0.003, Zeta potential: -33.60 ± 3.39 mV). Mannitol was selected for lyophilization. Lyo-NPs improved the stability of the NPs (1 year), wherein the physicochemical properties of the NPs were maintained (RDI was close to 1.0). An cytotoxicity assay of PTX combined with DHA showed a synergistic anticancer effect (CI <1.0). The suppressive effects of Lyo-NPs on tumor growth were dose-dependent. While the cocktail of free drugs showed high toxicity (7.5 mg PTX-15 mg DHA/kg) , Lyo-NPs showed no statistical differences in hematological and biochemical parameters compared to the control.
Dual-drug-loaded hybrid PLGA-lecithin NP is a potential system to minimize severe side effects while enhancing antitumor efficacy, in which lyophilization is a key process to increase stability.
抗癌治疗需要提供有效和安全的患者药物。本研究旨在开发和应用纳米粒子（NPs）用于癌症治疗。
紫杉醇（PTX）的溶解度差，由于制剂赋形剂引起的过敏副作用，限制了其治疗效果。为了克服这一问题，将 PTX 与青蒿素衍生物偶联并载入 NP 药物递送系统，以提高其效果，同时解决其低溶解度问题。
本研究制备并表征了一种含有二氢青蒿素（DHA）和 PTX 的混合 PLGA-卵磷脂 NP，用于协同抗癌治疗。冷冻干燥研究提高了 NP 药物制剂的稳定性。
采用单步溶剂蒸发法制备载双 PTX 和 DHA 的 PLGA-和卵磷脂 NPs。NP 混悬液经冷冻干燥，考察了冻干保护剂的种类和比例。对 NPs 和冻干饼（Lyo-NPs）的理化性质进行了表征。在 2-8°C 和室温条件下考察了 Lyo-NPs 的稳定性。采用体外细胞毒性试验和动物模型分析药物组合、NP 混悬液和冻干粉末的抗癌效果。
优化了载 PTX-DHA 的 PLGA-卵磷脂-NP 的配方（200nm，PDI：0.248±0.003，Zeta 电位：-33.60±3.39mV）。甘露醇被选为冻干保护剂。Lyo-NPs 提高了 NPs 的稳定性（1 年），其中 NPs 的理化性质得以维持（RDI 接近 1.0）。PTX 与 DHA 联合的细胞毒性试验显示出协同抗癌作用（CI<1.0）。Lyo-NPs 对肿瘤生长的抑制作用呈剂量依赖性。虽然游离药物混合物表现出高毒性（7.5mgPTX-15mgDHA/kg），但与对照组相比，Lyo-NPs 在血液学和生化学参数方面没有统计学差异。
载双药混合 PLGA-卵磷脂 NP 是一种有潜力的系统，可以在最小化严重副作用的同时增强抗肿瘤疗效，其中冷冻干燥是提高稳定性的关键过程。
