Scientific community is striving to understand the role of P-glycoprotein (P-gp) in drug discovery programs
due to its impact on pharmacokinetic and multi-drug resistance (MDR) of anticancer drugs. A number of efforts to resolve
the crystal structure and understanding the mechanism of P-gp mediated efflux have been made. Several generations of Pgp
inhibitors have been developed to tackle this multi-specific efflux protein. Unfortunately, these inhibitors lack
selectivity, exhibit poor solubility and severe pharmacokinetic interactions restricting their clinical use. The nanocarrier
drug delivery systems (NDDS) are receiving increasing attention for P-gp modulating activity of pharmaceutical
excipients which are used in their fabrication. In addition, NDDS can enhance the solubility and exhibited ability to
bypass P-gp mediated efflux. The co-formulation of P-gp inhibitors and substrate anticancer drugs in single drug delivery
system offers the advantage of bypassing P-gp mediated drug efflux as well as inhibiting the P-gp. Moreover, severe
pharmacokinetic interactions between P-gp inhibitor and substrate anticancer drugs could be avoided by using this
strategy. In this article we describe the co-formulation strategies using nanocarriers for modulation of pharmacokinetics as
well as multi-drug resistance of anticancer drugs along with the challenges in this area.
Keywords: Anticancer drugs, co-formulation, multi-drug resistance, nanocarriers, P-glycoprotein inhibitor.
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