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聚乙二醇化脂质体阿霉素与卡铂联合用药对胶质母细胞瘤的影响

Impact of PEGylated Liposomal Doxorubicin and Carboplatin Combination on Glioblastoma.

作者信息

Ghaferi Mohsen, Raza Aun, Koohi Maedeh, Zahra Warda, Akbarzadeh Azim, Ebrahimi Shahmabadi Hasan, Alavi Seyed Ebrahim

机构信息

Immunology of Infectious Diseases Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan 7717933777, Iran.

School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.

出版信息

Pharmaceutics. 2022 Oct 13;14(10):2183. doi: 10.3390/pharmaceutics14102183.

Abstract

Glioblastoma is an incurable cancer with a 5-year survival chance of less than 5%. Chemotherapy is a therapeutic approach to treating the disease; however, due to the presence of the blood-brain barrier (BBB), the probability of success is low. To overcome this issue, nanoparticles are promising carriers for crossing the BBB and delivering drugs to the tumor. In this study, the anticancer efficacy of doxorubicin (DOX) and carboplatin (CB) loaded into polyethylene glycol (PEG)ylated liposome nanoparticles (PEG-Lip) and in treating brain cancer was evaluated in vitro and in vivo. The results demonstrated that PEG-Lip-DOX/CB with a size of 212 ± 10 nm was synthesized that could release the loaded drugs in a controlled manner, from which 56.3% of the loaded drugs were released after 52 h. In addition, PEG-Lip-DOX/CB could significantly increase the cytotoxicity effects of the drugs against rat glioma C6 cells (IC: 8.7 and 12.9 µM for the drugs-loaded nanoparticles and DOX + CB, respectively). The in vivo results also demonstrated that PEGylated liposomes, compared to non-PEGylated liposomes (Lip) and DOX + CB, were more efficient in increasing the therapeutic effects and decreasing the side effects of the drugs, in which the survival times of the glioblastoma-bearing rats were 39, 35, and 30 days in the PEG-Lip-DOX/CB, Lip-DOX/CB, and DOX + CB receiver groups, respectively. In addition, the weight loss was found to be 8.7, 10.5, and 13%, respectively, in the groups. The results of the toxicity evaluation were also confirmed by histopathological studies. Overall, the results of this study demonstrated that the encapsulation of DOX and CB into PEG-Lip is a promising approach to improving the properties of DOX and CB in terms of their therapeutic effects and drug side effects for the treatment of glioblastoma.

摘要

胶质母细胞瘤是一种无法治愈的癌症,5年生存率不到5%。化疗是治疗该疾病的一种方法;然而,由于血脑屏障(BBB)的存在,成功的概率很低。为了克服这个问题,纳米颗粒有望成为穿越血脑屏障并将药物递送至肿瘤的载体。在本研究中,对负载于聚乙二醇(PEG)化脂质体纳米颗粒(PEG-Lip)中的阿霉素(DOX)和卡铂(CB)治疗脑癌的体外和体内抗癌疗效进行了评估。结果表明,合成了尺寸为212±10 nm的PEG-Lip-DOX/CB,其能够以可控方式释放负载的药物,52小时后释放了56.3%的负载药物。此外,PEG-Lip-DOX/CB可显著增加药物对大鼠胶质瘤C6细胞的细胞毒性作用(负载药物的纳米颗粒和DOX+CB的半数抑制浓度分别为8.7和12.9 μM)。体内结果还表明,与非PEG化脂质体(Lip)和DOX+CB相比,PEG化脂质体在提高治疗效果和降低药物副作用方面更有效,其中荷胶质母细胞瘤大鼠在PEG-Lip-DOX/CB、Lip-DOX/CB和DOX+CB接受组中的生存时间分别为39、35和30天。此外,各组的体重减轻分别为8.7%、10.5%和13%。毒性评估结果也通过组织病理学研究得到了证实。总体而言,本研究结果表明,将DOX和CB封装到PEG-Lip中是一种在治疗胶质母细胞瘤的治疗效果和药物副作用方面改善DOX和CB性质的有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31f5/9609487/bb00203871ac/pharmaceutics-14-02183-g001.jpg

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