Background: Drug delivery systems have demonstrated promising results to cross blood–brain barrier (BBB) and deliver the loaded therapeutics to the brain tumor. This study aims to utilize the transferrin receptor (TR)-targeted liposomal cisplatin (Cispt) for transporting Cispt across the BBB and deliver Cispt to the brain tumor.
Methods: Targeted pegylated liposomal cisplatin (TPL-Cispt) was synthesized using reverse phase evaporation method and thiolated OX26 monoclonal antibody. The formulation was characterized in terms of size, size distribution, zeta potential, drug encapsulation and loading efficiencies, bioactivity, drug release profile, stability and cellular uptake using dynamic light scattering, flame atomic absorption spectroscopy (AAS), ELISA, dialysis membrane, and fluorescence assay. Next, the potency of the formulation to increase the therapeutic effects of Cispt and decrease its toxicity effects was evaluated in the brain tumor-bearing rats through measuring the mean survival time (MST), blood factors and histopathological studies.
Results: The results showed that TPL-Cispt with a size of 157± 8 nm and drug encapsulation efficiency of 24%± 1.22 was synthesized, that was biologically active and released Cispt in a slow-controlled manner. The formulation compared to Cispt-loaded PEGylated liposome nanoparticles (PL-Cispt) caused an increase in the cellular uptake by 1.43-fold, as well as an increase in the MST of the brain tumor-bearing rats by 1.7-fold compared to the PL-Cispt (P< 0.001). TPL-Cispt was potent enough to cause a significant decrease in Cispt toxicity effects (P< 0.001).
Conclusion: Overall, the results suggest that targeting the Cispt-loaded PEGylated liposome is a promising approach to develop formulation with enhanced efficacy and reduced toxicity for the treatment of brain tumor.



中文翻译：

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使用靶向脂质体顺铂的体内胶质母细胞瘤治疗

背景：药物输送系统已显示出有希望的结果，可以穿过血脑屏障 (BBB) 并将负载的治疗药物输送到脑肿瘤。本研究旨在利用转铁蛋白受体 (TR) 靶向脂质体顺铂 (Cispt) 将 Cispt 转运穿过 BBB 并将 Cispt 递送至脑肿瘤。
方法：使用反相蒸发法和硫醇化 OX26 单克隆抗体合成靶向聚乙二醇化脂质体顺铂 (TPL-Cispt)。使用动态光散射、火焰原子吸收光谱 (AAS)、ELISA、透析膜和荧光检测。接下来，通过测量平均存活时间 (MST)、血液因子和组织病理学研究，在荷脑瘤大鼠中评估了该制剂增加 Cispt 治疗效果和降低其毒性作用的效力。
结果：结果表明，合成的TPL-Cispt尺寸为157±8 nm，药物包封率为24%±1.22，具有生物活性，缓控释放Cispt。与负载 Cispt 的聚乙二醇化脂质体纳米粒子 (PL-Cispt) 相比，该制剂导致细胞摄取增加 1.43 倍，以及与 PL 相比，脑肿瘤大鼠的 MST 增加 1.7 倍-Cispt ( P < 0.001)。TPL-Cispt 的效力足以显着降低 Cispt 的毒性作用 ( P < 0.001)。
结论：总体而言，结果表明，靶向装载 Cispt 的聚乙二醇化脂质体是开发用于治疗脑肿瘤的具有增强功效和降低毒性的制剂的有前景的方法。