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
dc.contributor.author | Mohamed, Elham A. | |
dc.contributor.author | Zhao, Yunqi | |
dc.contributor.author | Meshali, Mahasen M. | |
dc.contributor.author | Remsberg, Connie M. | |
dc.contributor.author | Borg, Thanaa M. | |
dc.contributor.author | Foda, Abdel Monem M. | |
dc.contributor.author | Takemoto, Jody K. | |
dc.contributor.author | Sayre, Casey | |
dc.contributor.author | Martinez, Stephanie A. | |
dc.contributor.author | Davies, Neal M. | |
dc.contributor.author | Forrest, M. Laird | |
dc.date.accessioned | 2017-04-26T19:44:44Z | |
dc.date.available | 2017-04-26T19:44:44Z | |
dc.date.issued | 2012-10 | |
dc.identifier.citation | Mohamed, 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.23265 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/23823 | |
dc.description.abstract | The 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.publisher | Elsevier | en_US |
dc.rights | 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. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Nanocarrier | en_US |
dc.subject | Pharmacokinetics | en_US |
dc.subject | Polymeric micelles | en_US |
dc.subject | PEG-b-PLA | en_US |
dc.title | 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 | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Zhao, Yunqi | |
kusw.kuauthor | Forrest, M. Laird | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
dc.identifier.doi | 10.1002/jps.23265 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC4699555 | en_US |
dc.rights.accessrights | openAccess |
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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.