University of Health Sciences Turkey, Gülhane Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Turkey.
University of Health Sciences Turkey, Gülhane Faculty of Pharmacy, Department of Pharmaceutical Technology Ankara, Turkey.
Food Chem Toxicol. 2021 Aug;154:112323. doi: 10.1016/j.fct.2021.112323. Epub 2021 Jun 7.
Neuroblastoma, a neoplasm of the sympathetic nervous system, is the second most common extracranial malignant tumor of childhood and the most common solid tumor of infancy. Paclitaxel (taxol), a diterpenoid pseudoalkaloid isolated from the shells of Taxus brevifolia, is the first taxane derivative used in the clinic for cancer treatment. Poly (lactic-co-glycolic acid) (PLGA) is one of the most successfully used biodegradable polymers for drug delivery which has a minimum systemic toxicity. This study aimed to evaluate the cytotoxicity and genotoxicity of paclitaxel nanoencapsulated with PLGA. Cytotoxic effects were determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and genotoxic effects were determined by single cell gel electrophoresis (Comet) method in human neuroblastoma cells (SH-SY5Y). According to our results, the viability of cells treated with concentrations higher than 10 nM of free paclitaxel and paclitaxel loaded PLGA nanoparticles for 48 and 72 h was found lower than 50%. Additionally, DNA damage increased with the increase of nanoparticle dose when the cells exposed to paclitaxel loaded PLGA nanoparticles for 24, 48 and 72 h. It can be concluded that PLGA nanoparticles can be considered as a biocompatible carrier system for drug delivery and might be promising agent against neuroblastoma.
神经母细胞瘤是交感神经系统的一种肿瘤，是儿童期第二常见的颅外恶性肿瘤，也是婴儿期最常见的实体瘤。紫杉醇（taxol）是从短叶红豆杉的树皮中分离出来的二萜类伪生物碱，是第一个用于癌症治疗的紫杉烷衍生物。聚（乳酸-共-乙醇酸）（PLGA）是用于药物输送的最成功的可生物降解聚合物之一，具有最小的全身毒性。本研究旨在评估紫杉醇与 PLGA 纳米囊泡包封后的细胞毒性和遗传毒性。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法测定细胞毒性，通过单细胞凝胶电泳（彗星）法测定人神经母细胞瘤细胞（SH-SY5Y）的遗传毒性。根据我们的结果，游离紫杉醇和紫杉醇负载 PLGA 纳米颗粒浓度高于 10 nM 时，细胞的存活率在 48 和 72 h 后低于 50%。此外，当细胞暴露于紫杉醇负载 PLGA 纳米颗粒 24、48 和 72 h 时，随着纳米颗粒剂量的增加，DNA 损伤也增加。综上所述，PLGA 纳米颗粒可被视为一种用于药物输送的生物相容性载体系统，可能是治疗神经母细胞瘤的有前途的药物。
