Investigation of the micellar effect of pluronic P85 on P-glycoprotein inhibition: Cell accumulation and equilibrium dialysis studies

Shaik Naveed, Giri Nagdeep, William F. Elmquist

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28 Scopus citations


The objective of this study was: (1) to characterize the P-gp inhibitory effect of different concentrations of Pluronic P85 on anti-HIV-1 drug cellular accumulation, and (2) to investigate the relationship between cellular accumulation and free fraction of drug. Cellular accumulation studies in MDCKII-WT and MDCKII-MDR1 cell monolayers showed a biphasic dose response characterized by decline in accumulation at Pluronic concentrations greater than the CMC. This phenomenon was independent of the inhibition of P-gp efflux by Pluronic. Cell-free equilibrium dialysis was used to determine the effect of Pluronic P85 on drug free fraction and the affinity of Pluronic micelles for drug was modeled. Nelfinavir and saquinavir associated extensively with micelles and equilibrium free fractions were low at P85 concentrations above the CMC, with association constants being in the order nelfinavir > saquinavir ⋙ abacavir. abacavir. Abacavir, a P-gp substrate, showed no association with micelles yet showed a biphasic response in cellular accumulation. These data suggest that, above the CMC, inhibition of P-gp is not affected but rather factors such as micellar trapping could contribute to decreased accumulation. Therefore, the in vitro evaluation of the effect of Pluronic formulations on active transport should take into account both the physicochemical properties of drug and the composition of Pluronic.

Original languageEnglish (US)
Pages (from-to)4170-4190
Number of pages21
JournalJournal of Pharmaceutical Sciences
Issue number11
StatePublished - Nov 2009

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grant NS42549. We thank Dr. Piet Borst from the Netherlands Cancer Institute for generously providing the parent MDCKII and P-gp over-expressing MDCKII cells. We would like to thank BASF for generously providing us with Pluronics and to GlaxoSmithKline for their gift of GF120198.


  • Critical micellar concentration
  • Efflux pumps
  • Equilibrium dialysis
  • HIV-1 protease inhibitors
  • Micelle
  • P-glycoprotein
  • Pluronics
  • Polymers


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