Gupta Preeti, Garg Tarun, Tanmay M, Arora Saahil
Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, India.
Department of Pharmaceutics, ISF College of Pharmacy, Moga (Punjab), India.
Crit Rev Ther Drug Carrier Syst. 2015;32(3):247-75. doi: 10.1615/critrevtherdrugcarriersyst.2015011592.
Permeability glycoprotein (P-gp), a multispecific drug transporter belonging to the multidrug resistance (MDR) gene subfamily, is mainly responsible for efflux of diffused intracellular drugs, resulting in poor drug bioavailability. P-gp is overexpressed in the blood-brain barrier, gastrointestinal tract (GIT), kidney, liver, pancreas, and cancerous cells, leading to multidrug resistance and failure of therapy. Because P-gp is transported into cells by way of receptor-mediated endocytosis (in contrast to diffusion for free drug), polymeric efflux pump modulators can have a major role in efficient drug delivery. Various polymer drug conjugates that have been proven to provide potential treatments in MDR cases are reviewed here, with an emphasis on the role of the P-gp efflux pump, bioavailability, and the mechanism of inhibition of the P-gp transporter by various polymers and delivery systems. This review also highlights the potential of specific polymer drug conjugates to act as P-gp efflux pump inhibitors to provide enhanced bioavailability and therapeutic efficacy.
通透性糖蛋白（P-糖蛋白）是一种属于多药耐药（MDR）基因亚家族的多特异性药物转运蛋白，主要负责细胞内扩散药物的外排，导致药物生物利用度差。P-糖蛋白在血脑屏障、胃肠道（GIT）、肾脏、肝脏、胰腺和癌细胞中过度表达，导致多药耐药和治疗失败。由于P-糖蛋白是通过受体介导的内吞作用进入细胞（与游离药物的扩散相反），聚合物外排泵调节剂在高效药物递送中可发挥重要作用。本文综述了各种已被证明可在多药耐药情况下提供潜在治疗方法的聚合物药物缀合物，重点关注P-糖蛋白外排泵的作用、生物利用度以及各种聚合物和递送系统对P-糖蛋白转运蛋白的抑制机制。本综述还强调了特定聚合物药物缀合物作为P-糖蛋白外排泵抑制剂以提高生物利用度和治疗效果的潜力。
