Kumar Rajendra, Kumar Pramod, Singh Bhupinder, Sharma Gajanand, Katare Om Prakash, Raza Kaisar
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Dist. Ajmer, Rajasthan, 305 817, India.
UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites, Panjab University, Chandigarh, 160 014, India.
Int J Pharm. 2017 Mar 15;519(1-2):138-144. doi: 10.1016/j.ijpharm.2017.01.021. Epub 2017 Jan 16.
Methotrexate (MTX) is a widely used drug for the management of various kinds of cancers. However, numerous challenges are associated with MTX like poor aqueous solubility, dose-dependent side effects and poor-bioavailability. With an aim to explore the potential benefits in drug delivery of MTX, it was intended to fabricate glycine-PLGA-based polymeric micelles. Glycine was chemically linked to PLGA and the linkage was confirmed by FT-IR, and NMR-Spectroscopy. The developed polymeric micelles offered substantial loading to MTX with a pH-dependent drug release profile. The drug was released maximally at the cancer cell pH vis-à-vis blood plasma pH. The cytotoxicity of drug against MDA-MB-231 cell lines was enhanced by approx. 100% and the confocal laser scanning microscopy confirmed the localization of dye-tagged nanocarriers in the interiors of cancer cells. The bioavailable fraction of the drug was increased by approx. 4-folds, whereas elimination half-life was enhanced by around two-folds in Wistar rats. The novel approach offers a biodegradable and promising carrier for the better delivery of anticancer agents with immense promises of efficacy enhancement, improved delivery and better pharmacokinetic profile.
甲氨蝶呤（MTX）是一种广泛用于治疗各类癌症的药物。然而，MTX存在诸多挑战，如较差的水溶性、剂量依赖性副作用和低生物利用度。为了探索MTX在药物递送方面的潜在益处，研究人员打算制备基于甘氨酸 - PLGA的聚合物胶束。甘氨酸通过化学方法与PLGA相连，通过傅里叶变换红外光谱（FT - IR）和核磁共振光谱（NMR）对该连接进行了确认。所制备的聚合物胶束对MTX具有大量载药量，并呈现出pH依赖性药物释放曲线。与血浆pH相比，该药物在癌细胞pH条件下释放量最大。药物对MDA - MB - 231细胞系的细胞毒性提高了约100%，共聚焦激光扫描显微镜证实了染料标记的纳米载体在癌细胞内部的定位。在Wistar大鼠中，该药物的生物利用分数提高了约4倍，消除半衰期延长了约两倍。这种新方法提供了一种可生物降解且有前景的载体，用于更好地递送抗癌药物，有望显著提高疗效、改善药物递送并具有更好的药代动力学特征。
