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基于透明质酸修饰的 PLGA 的纳米粒的制备及特性研究——提高顺铂在实体瘤中疗效的新策略。

Development and characterization of hyaluronic acid modified PLGA based nanoparticles for improved efficacy of cisplatin in solid tumor.

机构信息

Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.

Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.

出版信息

Biomed Pharmacother. 2017 Nov;95:856-864. doi: 10.1016/j.biopha.2017.08.108. Epub 2017 Sep 10.


DOI:10.1016/j.biopha.2017.08.108
PMID:28903181
Abstract

Cisplatin is a potent and widely used chemotherapeutic agent to treat a variety of tumors. However, its clinical use is associated with undesirable side effects and acquired resistance to cisplatin. In this study, cisplatin loaded hyaluronic acid (HA) functionalized poly (lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles (CP-HA-PLGA-PEG-NPs) were fabricated using double emulsion solvent evaporation method to target CD44 receptor expressed on cancerous cells. The developed nanoconstructs were characterized for various in vitro parameters, including size distribution, zeta potential, morphology, drug loading and in vitro release. The HA content on the HA-PLGA-PEG-NPs was quantified by a turbidimetric method. The in vitro anticancer study in human ovarian cancer (SKOV-3) cells showed significantly (p<0.05) higher cytotoxicity of CP-HA-PLGA-PEG NPs as compared to free cisplatin and non-targeted nanoparticles (CP-PLGA-PEG NPs). Further, laser scanning confocal microscopy revealed that there was enhanced cellular uptake of HA-PLGA-PEG NPs in CD44-over expressing ovarian cancer cell line (SKOV-3). The in vivo antitumor activity of CP-HA-PLGA-PEG-NPs was significantly (p<0.05) higher than free cisplatin and CP-PLGA-PEG-NPs in Ehrlich tumor (solid) bearing mice. The results demonstrated the potential of target specific nanoconstruct of cisplatin in the improved cancer chemotherapy.

摘要

顺铂是一种有效的、广泛应用于治疗多种肿瘤的化疗药物。然而,其临床应用与不良副作用和对顺铂的获得性耐药性有关。在这项研究中,采用双重乳液溶剂蒸发法制备了载顺铂的透明质酸(HA)功能化聚(乳酸-共-乙醇酸)-聚(乙二醇)纳米粒子(CP-HA-PLGA-PEG-NPs),以靶向癌细胞表面表达的 CD44 受体。对所开发的纳米结构进行了各种体外参数的表征,包括粒径分布、Zeta 电位、形态、药物负载和体外释放。通过浊度法定量测定 HA-PLGA-PEG-NPs 上的 HA 含量。体外抗癌研究表明,与游离顺铂和非靶向纳米粒子(CP-PLGA-PEG-NPs)相比,CP-HA-PLGA-PEG-NPs 对人卵巢癌细胞(SKOV-3)具有显著更高的细胞毒性(p<0.05)。进一步的激光扫描共聚焦显微镜显示,在 CD44 过表达的卵巢癌细胞系(SKOV-3)中,HA-PLGA-PEG-NPs 的细胞摄取增强。CP-HA-PLGA-PEG-NPs 在荷 Ehrlich 肿瘤(实体瘤)小鼠中的体内抗肿瘤活性明显(p<0.05)高于游离顺铂和 CP-PLGA-PEG-NPs。结果表明,载顺铂的靶向纳米结构具有改善癌症化疗的潜力。

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