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用于可持续和定点给药的深共晶溶剂介导的FA-β-丙氨酸-PCL药物载体

Deep Eutectic Solvent-Mediated FA--β-Alanine--PCL Drug Carrier for Sustainable and Site-Specific Drug Delivery.

作者信息

Pradeepkumar Periyakaruppan, Rajendran Naresh Kumar, Alarfaj Abdullah A, Munusamy Murugan A, Rajan Mariappan

机构信息

Biomaterials in Medicinal Chemistry Laboratory, Department of Natural Products Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, Tamil Nadu,India.

Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, Doornfontein 2028, South Africa.

出版信息

ACS Appl Bio Mater. 2018 Dec 17;1(6):2094-2109. doi: 10.1021/acsabm.8b00554. Epub 2018 Nov 27.

Abstract

An amphiphilic polymer that consisted of a deep eutectic solvent (DES)-mediated drug carrier was designed, where the DES influenced the formation of folic acid (FA)-tagged -β-alanine--PCL polymer (DES@FA--β-alanine--PCL); the nature of the carrier was investigated through emission analysis and pyrene used as a model probe (CMC = 0.4 mg/mL). The amphiphilic polymer was self-assembled into a sphere (≈204 nm diameter) with a surface charge of -3 ± 0.5 mV. The doxorubicin was incorporated and the structural changes were analyzed by UV-visible spectroscopy, FT-IR, XRD, Raman, and TGA analysis, while size and morphological analysis was performed by DLS, AFM, SEM, and TEM. The controlled release of drug from the carrier was observed at different pH levels. The enhanced anticancer potential of DOX-loaded polymeric micelle was studied both in vitro and in vivo breast cancer model. The treatment of DOX-loaded polymeric micelle reduces the viability and proliferation of MDA-MB-231 cells. From the results of the current investigation it concludes that the DOX-loaded polymeric micelle has enhance anticancer effect and it exhibits its potential effect at the dosage of 5 mg/kg body weight in mammary carcinoma-bearing rats. From the observed results, synthesized DOX-loaded polymeric micelle holds strong anticancer properties compared with free DOX and can be used as a potential carrier in the pharmaceutical industry.

摘要

设计了一种由深共熔溶剂(DES)介导的药物载体组成的两亲性聚合物,其中DES影响叶酸(FA)标记的-β-丙氨酸-聚己内酯聚合物(DES@FA-β-丙氨酸-聚己内酯)的形成;通过发射分析和使用芘作为模型探针(临界胶束浓度=0.4mg/mL)研究了载体的性质。两亲性聚合物自组装成直径约204nm、表面电荷为-3±0.5mV的球体。将阿霉素包封其中,并通过紫外可见光谱、傅里叶变换红外光谱、X射线衍射、拉曼光谱和热重分析对结构变化进行分析,同时通过动态光散射、原子力显微镜、扫描电子显微镜和透射电子显微镜进行尺寸和形态分析。在不同pH水平下观察到药物从载体中的控释。对载有阿霉素的聚合物胶束在体外和体内乳腺癌模型中的增强抗癌潜力进行了研究。载有阿霉素的聚合物胶束处理降低了MDA-MB-231细胞的活力和增殖。从当前研究结果得出结论,载有阿霉素的聚合物胶束具有增强的抗癌作用,并且在荷乳腺癌大鼠中以5mg/kg体重的剂量表现出其潜在效果。从观察结果来看,合成的载有阿霉素的聚合物胶束与游离阿霉素相比具有很强的抗癌性能,可作为制药行业的潜在载体。

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