title: The emerging role of P-glycoprotein inhibitors in drug delivery: a patent review.
abstract: BACKGROUND
  The ATP-binding cassette superfamily contains membrane transporter proteins that transport a wide range of diverse compounds across cellular membranes. The P-glycoprotein (P-gp) is an important member of this family and a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of many clinically active drugs. The inhibition of this efflux transporter by various P-gp inhibitors forms a distinctive approach in improving bioavailability and conquering drug resistance. Most P-gp inhibitors exhibit limitations associated with their safety and unwanted pharmacokinetic interactions, thereby restraining their clinical applicability.
  
  
  METHODS
  This review explores the investigations on the feasibility and applicability of various classes of P-gp inhibitors as described in recent patents for enhanced drug delivery.
  
  
  CONCLUSIONS
  Several candidates presently under development look promising as P-gp inhibitors, e.g., tariquidar and elacridar. Pharmaceutical excipients currently constitute the most promising class of P-gp inhibitors and are considered safe and pharmaceutically acceptable for use in formulations. In addition, lipid-based excipients and thiolated polymers play an active role in affecting P-gp-mediated transport not only by altering the membrane fluidity or ATPase activity but by down regulating P-gp expression. An additional overture such as the prodrug derivatization of P-gp substrates is a feasible approach to bypass P-gp-mediated efflux.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard Hamdard University, New Delhi 110062, India.
authors.forename: Naseem
authors.initials: N
authors.lastname: Akhtar
authors.forename: Abdul
authors.initials: A
authors.lastname: Ahad
authors.forename: Roop Kishan
authors.initials: RK
authors.lastname: Khar
authors.forename: Manu
authors.initials: M
authors.lastname: Jaggi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Aqil
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.forename: Farhan Jalees
authors.initials: FJ
authors.lastname: Ahmad
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D016503:Drug Delivery Systems; D005079:Excipients / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D010330:Patents as Topic; D011108:Polymers / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D005079:Excipients; D007166:Immunosuppressive Agents; D011108:Polymers; D013501:Surface-Active Agents