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dc.contributor.authorMohamed, Elham A.
dc.contributor.authorZhao, Yunqi
dc.contributor.authorMeshali, Mahasen M.
dc.contributor.authorRemsberg, Connie M.
dc.contributor.authorBorg, Thanaa M.
dc.contributor.authorFoda, Abdel Monem M.
dc.contributor.authorTakemoto, Jody K.
dc.contributor.authorSayre, Casey
dc.contributor.authorMartinez, Stephanie A.
dc.contributor.authorDavies, Neal M.
dc.contributor.authorForrest, M. Laird
dc.date.accessioned2017-04-26T19:44:44Z
dc.date.available2017-04-26T19:44:44Z
dc.date.issued2012-10
dc.identifier.citationMohamed, E. A., Zhao, Y., Meshali, M. M., Remsberg, C. M., Borg, T. M., Foda, A. M. M., … Forrest, M. L. (2012). Vorinostat with Sustained Exposure and High Solubility in Poly(ethylene glycol)-b-poly(DL-lactic acid) Micelle Nanocarriers: Characterization and Effects on Pharmacokinetics in Rat Serum and Urine. Journal of Pharmaceutical Sciences, 101(10), 3787–3798. http://doi.org/10.1002/jps.23265en_US
dc.identifier.urihttp://hdl.handle.net/1808/23823
dc.description.abstractThe histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anti-cancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)-b-poly(DL-lactic acid) (PEG-b-PLA) micelles of vorinostat were developed. Vorinostat’s pharmacokinetics in rats were investigated after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) micellar administrations and compared to a conventional PEG400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 mg/ml to 8.15 ± 0.60 mg/ml and 10.24 ± 0.92 mg/ml at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 nm and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19 %, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half-life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG-b-PLA micelles significantly improved the oral and intravenous pharmacokinetics and bioavailability of vorinostat, which warrants further investigation.en_US
dc.publisherElsevieren_US
dc.rightsThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subjectNanocarrieren_US
dc.subjectPharmacokineticsen_US
dc.subjectPolymeric micellesen_US
dc.subjectPEG-b-PLAen_US
dc.titleVorinostat with Sustained Exposure and High Solubility in Poly(ethylene glycol)-b-poly(DL-lactic acid) Micelle Nanocarriers: Characterization and Effects on Pharmacokinetics in Rat Serum and Urineen_US
dc.typeArticleen_US
kusw.kuauthorZhao, Yunqi
kusw.kuauthorForrest, M. Laird
kusw.kudepartmentPharmaceutical Chemistryen_US
dc.identifier.doi10.1002/jps.23265en_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC4699555en_US
dc.rights.accessrightsopenAccess


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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Except where otherwise noted, this item's license is described as: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License 4.0 (CC BY-NC-ND 4.0), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.