Department of Neurosciences, Biomedicine and Movement Sciences, Section of Anatomy and Histology, University of Verona, Strada Le Grazie, 8 - 37134 Verona, Italy.
Department of Neurosciences, Biomedicine and Movement Sciences, Section of Clinical Neurology, University of Verona, P.le L.A. Scuro, 10 - 37134 Verona, Italy.
Int J Pharm. 2019 Apr 5;560:347-356. doi: 10.1016/j.ijpharm.2019.02.017. Epub 2019 Feb 20.
The use of nanoparticles as drug carriers in the field of skeletal muscle diseases has been poorly addressed and the interaction of nanoparticles with skeletal muscle cells has been investigated almost exclusively on C2C12 murine myoblasts. In this study we investigated the effects poly(lactide-co-glycolide) nanoparticles, mesoporous silica nanoparticles and liposomes, on the viability of primary human myoblasts and analyzed their cellular uptake and intracellular distribution in both primary human myoblasts and myotubes. Our data demonstrate that poly(lactide-co-glycolide) nanoparticles do not negatively affect myoblasts viability, contrarily to mesoporous silica nanoparticles and liposomes that induce a decrease in cell viability at the highest doses and longest incubation time. Poly(lactide-co-glycolide) nanoparticles and mesoporous silica nanoparticles are internalized by endocytosis, poly(lactide-co-glycolide) nanoparticles undergo endosomal escape whereas mesoporous silica nanoparticles always occur within vacuoles. Liposomes were rarely observed within the cells. The uptake of all tested nanoparticles was less prominent in primary human myotubes as compared to myoblasts. Our findings represent the first step toward the characterization of the interaction between nanoparticles and primary human muscle cells and suggest that poly(lactide-co-glycolide) nanoparticles might find an application for drug delivery to skeletal muscle.
将纳米颗粒作为药物载体应用于骨骼肌疾病领域的研究还很少,而且纳米颗粒与骨骼肌细胞的相互作用几乎仅在 C2C12 鼠肌母细胞上进行了研究。在这项研究中,我们研究了聚(乳酸-共-乙醇酸)纳米颗粒、介孔硅纳米颗粒和脂质体对原代人肌母细胞活力的影响,并分析了它们在原代人肌母细胞和肌管中的细胞摄取和细胞内分布。我们的数据表明,聚(乳酸-共-乙醇酸)纳米颗粒不会对肌母细胞活力产生负面影响,而介孔硅纳米颗粒和脂质体在最高剂量和最长孵育时间下会导致细胞活力下降。聚(乳酸-共-乙醇酸)纳米颗粒和介孔硅纳米颗粒通过内吞作用被内化,聚(乳酸-共-乙醇酸)纳米颗粒经历内涵体逃逸,而介孔硅纳米颗粒总是存在于空泡中。脂质体很少在细胞内观察到。与肌母细胞相比,所有测试的纳米颗粒在原代人肌管中的摄取都不明显。我们的发现代表了对纳米颗粒与原代人肌肉细胞相互作用进行表征的第一步,并表明聚(乳酸-共-乙醇酸)纳米颗粒可能在将药物递送至骨骼肌方面有应用前景。