Novel formulation approaches for optimising delivery of anticancer drugs based on P-glycoprotein modulation

Drug Discov Today. 2009 Nov;14(21-22):1067-74. doi: 10.1016/j.drudis.2009.07.010. Epub 2009 Aug 6.

Abstract

Considerable research efforts have been directed towards understanding the enigma of P-glycoprotein (P-gp) in drug development and delivery. P-gp is a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of various anti-cancer drugs. Modulation of this efflux transporter by various traditional 'chemosensitisers' forms a distinctive approach in improving pharmacokinetics and conquering drug resistance. However, such inhibitors show limitations associated with their safety and unwanted pharmacokinetic drug interaction restraining their clinical applicability. To address these concerns, several research groups have used pharmaceutical excipients (functional excipients or additives) to inhibit P-gp and enhance drug permeability. This article focuses on such excipients, various co-development strategies for the formulation of cytotoxic drugs with this multi-drug resistance (MDR) reversing additives.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology*
  • Chemistry, Pharmaceutical
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm
  • Excipients
  • Humans

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Excipients