Co-formulation of P-glycoprotein Substrate and Inhibitor in Nanocarriers: An Emerging Strategy for Cancer Chemotherapy
Ankit Saneja, Ravindra Dhar Dubey, Noor Alam, Vaibhav Khare and Prem N. GuptaAffiliation:
Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu-Tawi-180001, India.
AbstractScientific 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.
Anticancer drugs, co-formulation, multi-drug resistance, nanocarriers, P-glycoprotein inhibitor.
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