Micro-145 下调经常在乳腺癌中发现，表明其作为治疗靶点的潜力。将外源性 miR-145 直接引入肿瘤部位一直是一个障碍，因为递送有限、生物利用度低，因此治疗效果较低。因此，本研究旨在合成并表征共同负载 Dox-HCl 和 miR-145 模拟物的聚乙二醇化脂质体，以研究其对 MDA-MB-231 细胞的体外抗增殖活性。该制剂采用复合中心设计来开发，以优化 Dox-HCl 和 miR-145 模拟物的纳米颗粒尺寸和封装效率 (EE%)。优化后的配方表现出最高的合意性函数 (D = 0.814)，并在 4°C 下 60 天内表现出优异的稳定性，保持稳定的纳米颗粒尺寸和 zeta 电位，最终的 Dox-HCl 和 miR-145 模拟物的相对 EE%孵化天数分别为 94.97±0.53% 和 51.96±2.67%。该系统在酸性条件下孵育 4 小时内显示出较高的药物释放速率。此外，与游离 Dox-HCl 和 miR-145 方案（IC50 = 1.00μM）相比，优化的制剂对 MDA-MB-231 细胞具有更高的毒性（IC50 = 0.58μM）。我们的研究结果表明，聚乙二醇化脂质体可以有效地将抗癌药物和治疗性 miRNA 同步递送到肿瘤细胞中，因此有必要进行进一步研究。

Micro-145 down-regulation is frequently found in breast cancers, indicating its potential as a therapeutic target. The introduction of exogenous miR-145 directly to the tumor sites has been a hurdle due to limited delivery, low bioavailability, and hence lower therapeutic efficacy. Thus, this study aims to synthesize and characterize PEGylated liposome co-loaded with Dox-HCl and miR-145 mimics to investigate its in-vitro anti-proliferative activity against MDA-MB-231 cells. The formulations were developed using a composite central design to optimize nanoparticle size and encapsulation efficiency (EE%) of Dox-HCl and miR-145 mimics. The optimized formulation exhibited the highest desirability function (D = 0.814) and displayed excellent stability over 60 days at 4 °C, maintaining a stable nanoparticle size and zeta potential, with relative EE% of Dox-HCl and miR-145 mimics on the final incubation day 94.97 ± 0.53% and 51.96 ± 2.67%, respectively. The system displayed a higher rate of drug release within 4 h of incubation at an acidic condition. Additionally, the optimized formulation demonstrated a higher toxicity (IC50 = 0.58 μM) against MDA-MB-231 cells than the free Dox- HCl and miR-145 regimen (IC50 = 1.00 μM). Our findings suggest that PEGylated liposome is tunable for effective concurrent delivery of anticancer drugs and therapeutic miRNAs into tumor cells, necessitating further investigation.