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顺铂和阿霉素负载脂质体的制备、表征及其共递送以增强抗癌活性

Preparation, characterization, and Co-delivery of cisplatin and doxorubicin-loaded liposomes to enhance anticancer Activities.

作者信息

Bahrami Parsa Mahdi, Tafvizi Farzaneh, Chaleshi Vahid, Ebadi Mostafa

机构信息

Department of Biology, Parand Branch, Islamic Azad University, Parand, Iran.

Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Disease, Shahid Beheshti University of Medical Science, Tehran, Iran.

出版信息

Heliyon. 2023 Oct 5;9(10):e20657. doi: 10.1016/j.heliyon.2023.e20657. eCollection 2023 Oct.

Abstract

Ovarian cancer stands as a leading cause of cancer-related deaths among women globally. This malignancy has hindered successful treatment attempts due to its inherent resistance to chemotherapy agents. The utilization of cisplatin and doxorubicin-loaded liposomes emerges as a strategically advantageous approach in the realm of biomedical applications. This strategy holds promise for augmenting drug efficacy, mitigating toxicity, refining pharmacokinetics, and facilitating versatile drug delivery while accommodating combination therapies. In pursuit of scholarly investigations, the eminent databases, including PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar, were meticulously scrutinized. Within this study, a nano-liposomal formulation was meticulously designed to serve as a co-delivery system. This system was optimized by varying lipid concentrations, hydration time, and DSPC: cholesterol molar ratios to efficiently encapsulate and load doxorubicin (DOX) and cisplatin (CIS) to overcome drug resistance problems. The Lipo (CIS + DOX) formulation underwent rigorous characterization including dimensions, entrapment efficiencies and drug release kinetics. Notably, the entrapment efficiency of cisplatin and doxorubicin loaded liposomal nanoparticles was an impressive 85.29 ± 1.45 % and 73.62 ± 1.70 %, respectively. Furthermore, Lipo (CIS + DOX) drug release kinetics exhibited pH-dependent properties, with lower drug release rates at physiological pH (7.4) than acidic (pH 5.4). Subsequent cytotoxicity assays revealed the enhanced biocompatibility of dual-drug liposomes with HFF cells compared to free drug combinations. Impressively, CIS and DOX-loaded liposomes induced significant cytotoxicity against A2780 in comparison to free drugs and combinatorial free drugs. Furthermore, the CIS and DOX-loaded liposome showed induced apoptotic potential and cell cycle arrest in A2780 compared to CIS, DOX, and their combination (CIS + DOX). Combining CIS and DOX via liposomal nanoparticles introduces a promising therapeutic avenue for addressing ovarian cancer. These nano-scale carriers hold the potential for attenuating the untoward effects of singular drugs and their attendant toxicities.

摘要

卵巢癌是全球女性癌症相关死亡的主要原因之一。这种恶性肿瘤因其对化疗药物固有的耐药性而阻碍了治疗的成功尝试。在生物医学应用领域,使用负载顺铂和阿霉素的脂质体是一种具有战略优势的方法。该策略有望提高药物疗效、减轻毒性、优化药代动力学,并在适应联合治疗的同时促进多功能药物递送。为了进行学术研究,对包括PubMed/MEDLINE、ScienceDirect、Scopus和谷歌学术在内的著名数据库进行了仔细审查。在本研究中,精心设计了一种纳米脂质体制剂作为共递送系统。通过改变脂质浓度、水化时间和DSPC:胆固醇摩尔比来优化该系统,以有效包封和负载阿霉素(DOX)和顺铂(CIS),从而克服耐药性问题。对脂质体(CIS + DOX)制剂进行了严格的表征,包括尺寸、包封效率和药物释放动力学。值得注意的是,负载顺铂和阿霉素的脂质体纳米颗粒的包封效率分别高达85.29±1.45%和73.62±1.70%。此外,脂质体(CIS + DOX)的药物释放动力学表现出pH依赖性,在生理pH(7.4)下的药物释放速率低于酸性(pH 5.4)。随后的细胞毒性试验表明,与游离药物组合相比,双药脂质体与HFF细胞的生物相容性增强。令人印象深刻的是,与游离药物和联合游离药物相比,负载CIS和DOX的脂质体对A2780细胞具有显著的细胞毒性。此外,与CIS、DOX及其组合(CIS + DOX)相比,负载CIS和DOX的脂质体在A2780细胞中表现出诱导凋亡的潜力和细胞周期阻滞。通过脂质体纳米颗粒将CIS和DOX联合使用为治疗卵巢癌引入了一条有前景的治疗途径。这些纳米级载体有可能减轻单一药物的不良影响及其伴随的毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d815/10560846/8c8777e7cce4/ga1.jpg

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