pgp - publications

Predict more pgp - ligand interactions now!

1. J Control Release. 2012 Apr 27. [Epub ahead of print]

Delivery of P-glycoprotein substrates using chemosensitizers and nanotechnology
for selective and efficient therapeutic outcomes.

Montesinos RN, Béduneau A, Pellequer Y, Lamprecht A.

Laboratory of Pharmaceutical Engineering, University of Franche-Comté, Besançon,

As a result of its broad substrate specificity and critical localization in
excretory and barrier function tissues, P-glycoprotein (P-gp) plays major roles
in the pharmacokinetics, safety and efficacy profiles of numerous drugs. P-gp is
often responsible for the failure of many chemical treatments against cancer,
immunosuppressive, infectious and neurodegenerative diseases. Among the
therapeutic approaches to circumvent P-gp function, advances in the design of new
chemical P-gp modulators to interact specifically with P-gp have yielded few
clinical successful reports. Members of a class of components that were initially
developed as surface active agents showed promising results with regard to the
modulation of P-gp. These components include surfactants and amphiphilic
co-polymers. Alternatively, colloidal systems were developed to facilitate drug
uptake in resistant cells. This approach is based on the encapsulation of drugs,
which masks them from the biological environment and prevents their transport by
P-gp using the surfactants released from the nanocarrier. Likewise, a novel and
synergistic strategy is currently being explored and involves
nanocarrier-mediated transport and controlled release of both P-gp substrates and
P-gp modulators. In this review, we discuss recent results obtained by direct
modulation with chemosensitizers and the available nanotechnology to modulate
P-gp function. In this manuscript, we also discuss unexplored pathways for future

Copyright © 2012. Published by Elsevier B.V.

PMID: 22562066 [PubMed - as supplied by publisher]