Mohammadi Zahra Ali, Aghamiri Seyed Foad, Zarrabi Ali, Talaie Mohammad Reza
Department of Chemical Engineering Faculty of Engineering, University of Isfahan, Hezar-Jerib Ave., Isfahan, 81746-73441, Iran.
Curr Drug Deliv. 2016;13(7):1065-1070. doi: 10.2174/1567201813666151228104643.
Liposomes can serve as promising carriers for targeting delivery and controlled release of anti-cancer drugs. Doxorubicin-loaded liposomes have achieved enhanced efficacy in some solid tumors due to EPR effect with prolonged circulation and reduced toxicity. In this study the effects of liposomal structure have been investigated on the loading efficiency and controlled release behavior. Liposomes with various compositions were prepared through a thin film hydration method, and extruded to large unilamellar vesicles (LUVs) with mean particle size (Z ave~ 100 nm) by high-pressure extrusion technique. Then, doxorubicin was loaded into liposomes using remote active loading strategy. The loading efficiency and drug release behavior were evaluated using various parameters such as medium pH, liposome compositions and cholesterol concentrations. Liposomes prepared with different compositions showed high levels of drug encapsulation. Drug loading efficiencies (>90%) achieved with high final drug/lipid ratio (0.18-0.2). Faster release was observed at pH 5.5 when compared to pH 7.4 for all formulations. The fastest release rate was observed for unsaturated lipid (<48hr) and the slowest release rate was observed for saturated lipids with high phase transition temperature such as 1, 2-distearoylphosphatidylcholine (DSPC) and hydrogenated soy phosphatidylcholine (HSPC) (10-18 days). The sustained release was observed for liposomal formulations containing cholesterol. In conclusion, we have demonstrated that drug release rate could be controlled by manipulating the composition of liposomal structures.
脂质体可作为有前景的载体，用于抗癌药物的靶向递送和控释。由于具有延长循环时间和降低毒性的增强渗透滞留（EPR）效应，载有多柔比星的脂质体在某些实体瘤中已实现疗效增强。在本研究中，研究了脂质体结构对载药效率和控释行为的影响。通过薄膜水化法制备了具有不同组成的脂质体，并通过高压挤压技术将其挤压成平均粒径（Z平均~100nm）的大单层囊泡（LUVs）。然后，采用远程主动载药策略将多柔比星载入脂质体。使用各种参数（如介质pH值、脂质体组成和胆固醇浓度）评估载药效率和药物释放行为。用不同组成制备的脂质体显示出高水平的药物包封。在最终药物/脂质比高（0.18 - 0.2）时实现了较高的载药效率（>90%）。对于所有制剂，在pH 5.5时观察到的释放速度比pH 7.4时更快。对于不饱和脂质观察到最快的释放速率（<48小时），而对于具有高相变温度的饱和脂质，如1,2 - 二硬脂酰磷脂酰胆碱（DSPC）和氢化大豆磷脂酰胆碱（HSPC），观察到最慢的释放速率（10 - 18天）。对于含有胆固醇的脂质体制剂观察到了缓释。总之，我们已经证明可以通过操纵脂质体结构组成来控制药物释放速率。
