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Pharmaceutics 2013, 5(1), 81-93; doi:10.3390/pharmaceutics5010081

Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat

1 College of Pharmacy, Department of Pharmaceutical Sciences, Washington State University, Pullman, WA 99163, USA 2 Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA 3 Faculty of Pharmacy, University of Manitoba, Winnipeg R3T 2N2, Canada
* Author to whom correspondence should be addressed.
Received: 13 November 2012 / Revised: 20 December 2012 / Accepted: 21 December 2012 / Published: 27 December 2012
(This article belongs to the Special Issue Micellar Drug Delivery)
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The rapamycin analog, ridaforolimus, has demonstrated potent anti-proliferative effects in cancer treatment, and it currently is being evaluated in a range of clinical cancer studies. Ridaforolimus is an extremely lipophilic compound with limited aqueous solubility, which may benefit from formulation with polymeric micelles. Herein, we report the encapsulation of ridaforolimus in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000) (DSPE-PEG2000) via a solvent extraction technique. Micelle loading greatly improved the solubility of ridaforolimus by approximately 40 times from 200 μg/mL to 8.9 mg/mL. The diameters of the drug-loaded micelles were 33 ± 15 nm indicating they are of appropriate size to accumulate within the tumor site via the enhanced permeability and retention (EPR) effect. The DSPE-PEG2000 micelle formulation was dosed intravenously to rats at 10 mg/kg and compared to a control of ridaforolimus in ethanol/PEG 400. The micelle significantly increased the half-life of ridaforolimus by 170% and decreased the clearance by 58%, which is consistent with improved retention of the drug in the plasma by the micelle formulation.
Keywords: ridaforolimus; preclinical pharmacokinetics; polymeric micelle; DSPE-PEG2000 ridaforolimus; preclinical pharmacokinetics; polymeric micelle; DSPE-PEG2000
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Remsberg, C.M.; Zhao, Y.; Takemoto, J.K.; Bertram, R.M.; Davies, N.M.; Forrest, M.L. Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat. Pharmaceutics 2013, 5, 81-93.

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