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

dc.contributor.authorRemsberg, Connie M.
dc.contributor.authorZhao, Yunqi
dc.contributor.authorTakemoto, Jody K.
dc.contributor.authorBertram, Rebecca M.
dc.contributor.authorDavies, Neal M.
dc.contributor.authorForrest, M. Laird
dc.date.accessioned2014-04-14T14:28:07Z
dc.date.available2014-04-14T14:28:07Z
dc.date.issued2012-12-27
dc.identifier.citationRemsberg, Connie M, Yunqi Zhao, Jody K Takemoto, Rebecca M Bertram, Neal M Davies, and Marcus Laird Forrest. 2012. “Pharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat.” Pharmaceutics 5 (1): 81–93. http://dx.doi.org/10.3390/pharmaceutics5010081
dc.identifier.urihttp://hdl.handle.net/1808/13477
dc.description.abstractThe 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.
dc.publisherMDPI
dc.rightsThis article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/)
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.subjectRidaforolimus
dc.subjectPreclinical pharmacokinetics
dc.subjectPolymeric micelle
dc.subjectDspe-peg2000
dc.titlePharmacokinetic Evaluation of a DSPE-PEG2000 Micellar Formulation of Ridaforolimus in Rat
dc.typeArticle
kusw.kuauthorZhao, Yunqi
kusw.kuauthorForrest, M. Laird
kusw.kudepartmentPharmaceutical Chemistry
dc.identifier.doi10.3390/pharmaceutics5010081
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/)
Except where otherwise noted, this item's license is described as: This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/)