Laboratorio de Biomembranas, Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, Bernal, Buenos Aires, Argentina.
J Liposome Res. 2010 Sep;20(3):191-201. doi: 10.3109/08982100903244518.
In this work, we analyzed protein interaction, cell toxicity, and biodistribution of liposome formulation for further possible applications as DNA vehicles in gene-therapy protocols. In relation to protein interaction, cationic liposomes showed the lowest protein interaction, but this parameter was incremented with DNA association. On the other hand, noncharged liposomes presented high protein interaction, but DNA association decreased this parameter. Protein interaction of polymeric liposomes did not change with DNA association. Cell toxicity of these three liposome formulations was low, cell death became present at concentrations higher than 0.5 mg/mL, and these concentrations were higher than those usually used in transfection assays. In the case of noncharged and polymeric liposomes, toxicity increased upon interaction with serum proteins. DNA/liposome-mediated tissue distribution was analyzed in Balb-c female mice. Results indicated that noncharged liposomes were able to deliver DNA to liver after intraperitoneal (i.p.) inoculation, while polymeric liposomes were able to deliver DNA to kidney by using the same inoculation route. Cationic liposomes were able to deliver DNA to a wide range of tissues by the i.p. route (e.g., liver, intestine, kidney, and blood). After subcutaneous inoculation, only cationic liposomes were able to deliver DNA to blood, but not the other two formulations within the detection limits of the method.
在这项工作中,我们分析了脂质体制剂的蛋白质相互作用、细胞毒性和生物分布,以进一步将其作为基因治疗方案中的 DNA 载体进行可能的应用。关于蛋白质相互作用,阳离子脂质体显示出最低的蛋白质相互作用,但与 DNA 结合后,这个参数增加了。另一方面,不带电荷的脂质体具有很高的蛋白质相互作用,但 DNA 结合降低了这个参数。聚合物脂质体的蛋白质相互作用不随 DNA 结合而变化。这三种脂质体制剂的细胞毒性较低,细胞死亡出现在浓度高于 0.5mg/mL 时,而这些浓度高于转染实验中通常使用的浓度。在非带电和聚合物脂质体的情况下,与血清蛋白相互作用后毒性增加。在 Balb-c 雌性小鼠中分析了 DNA/脂质体介导的组织分布。结果表明,非带电脂质体能够在腹腔内接种后将 DNA 递送到肝脏,而聚合物脂质体能够通过相同的接种途径将 DNA 递送到肾脏。阳离子脂质体能够通过腹腔内途径将 DNA 递送到广泛的组织中(例如肝脏、肠道、肾脏和血液)。皮下接种后,只有阳离子脂质体能够将 DNA 递送到血液中,而其他两种制剂在该方法的检测限内无法检测到。