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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 …