Khan Iliyas, Joshi Gaurav, Sarkar Bibekananda, Nakhate Kartik T, Mantha Anil K, Kumar Raj, Kaul Ankur, Chaturvedi Shubhra, Mishra Anil K, Gupta Umesh
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan 305817, India.
Department of Pharmaceutical Sciences and Natural Products, School of Basic and Applied Sciences, Central University of Punjab, Bathinda 151001, India.
ACS Appl Bio Mater. 2020 Nov 16;3(11):7789-7799. doi: 10.1021/acsabm.0c00974. Epub 2020 Oct 30.
Development of a biodegradable nanoplatform poly(lactic--glycolic acid) (PLGA) for co-delivery of two drugs is hugely imperative and beneficial in anticancer therapeutics. In this study, co-delivery of a natural phytoconstituent, crocin (carotenoid), and a commonly prescribed drug, doxorubicin, was attempted using a nanoparticulate platform in the form of PLGA nanoparticles. Doxorubicin was chemically conjugated, while crocin was encapsulated physically in prepared PLGA nanoparticles (PDCR NPs). Prepared NPs were well-characterized for size, ζ, and surface morphology. PDCR NPs were of 174.2 ± 1.57 nm in size. The transmission electron microscopy (TEM) and atomic force microscopy (AFM) images revealed the spherical shape and smooth surface morphology of the nanoparticles, respectively. The entrapment efficiency and drug loading were found to be 58.95 ± 2.58 and 13.89 ± 1.09%, respectively. The drug release pattern of PDCR NPs showed a sustained and controlled release pattern throughout 48 h in PBS buffer pH 7.4 and acetate buffer pH 6.5. PDCR NPs were significantly less hemolytic than doxorubicin ( < 0.0001). Investigational formulation selectively produced cytotoxic effects on breast cancer cells decreasing reactive oxygen species (ROS) and altering the mitochondrial potential that led to apoptosis with cell-cycle arrest at the G2/M phase. Prepared NPs were able to upregulate the caspase levels as well as efficient uptake by cells in a time-dependent manner. plasma drug profile studies in healthy rats revealed prolonged persistence of crocin and doxorubicin in systemic circulation. Additionally, the PDCR NPs portrayed reduced tumor volume as compared to control groups in the tumor-induced animal studies, which were favorable. Conclusively, the co-delivery of natural anticancer bioactive crocin along with doxorubicin in PDCR NPs provides a possible controlled-release nanoplatform for efficient drug delivery and .
开发一种用于共递送两种药物的可生物降解纳米平台聚乳酸 - 乙醇酸共聚物（PLGA）在抗癌治疗中极为必要且有益。在本研究中，尝试使用PLGA纳米颗粒形式的纳米颗粒平台共递送天然植物成分藏红花素（类胡萝卜素）和常用处方药阿霉素。阿霉素通过化学偶联，而藏红花素则物理包裹在制备的PLGA纳米颗粒（PDCR NPs）中。制备的纳米颗粒在尺寸、ζ电位和表面形态方面得到了很好的表征。PDCR NPs的尺寸为174.2±1.57 nm。透射电子显微镜（TEM）和原子力显微镜（AFM）图像分别显示了纳米颗粒的球形形状和光滑表面形态。包封率和载药量分别为58.95±2.58%和13.89±1.09%。PDCR NPs的药物释放模式在pH 7.4的PBS缓冲液和pH 6.5的醋酸盐缓冲液中48小时内呈现持续且可控的释放模式。PDCR NPs的溶血率明显低于阿霉素（<0.0001）。研究制剂对乳腺癌细胞选择性产生细胞毒性作用，降低活性氧（ROS）水平并改变线粒体电位，导致细胞凋亡并使细胞周期停滞在G2/M期。制备的纳米颗粒能够以时间依赖性方式上调半胱天冬酶水平并被细胞有效摄取。健康大鼠的血浆药物分布研究表明藏红花素和阿霉素在体循环中的持续时间延长。此外，在肿瘤诱导的动物研究中，与对照组相比，PDCR NPs的肿瘤体积减小，这是有利的。总之，在PDCR NPs中共递送天然抗癌生物活性成分藏红花素和阿霉素提供了一种可能的控释纳米平台，用于高效药物递送。
