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.
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.
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
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please
share your stories
about how Open Access to this item benefits YOU.
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.
The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.