Development of Vorinostat-Loaded Solid Lipid Nanoparticles to Enhance Pharmacokinetics and Efficacy against Multidrug-Resistant Cancer Cells

Title
Development of Vorinostat-Loaded Solid Lipid Nanoparticles to Enhance Pharmacokinetics and Efficacy against Multidrug-Resistant Cancer Cells
Author(s)
김종오트란탄힙티르거네쉬라마사미트롱두이히유신범수[신범수]최한곤[최한곤]용철순
Keywords
HISTONE DEACETYLASE INHIBITORS; SUBEROYLANILIDE HYDROXAMIC ACID; ANTICANCER DRUG-DELIVERY; TRANS-RETINOIC ACID; PHYSICOCHEMICAL CHARACTERIZATION; IMPROVE ENCAPSULATION; ANTITUMOR-ACTIVITY; FORMULATION; CARRIERS; DOCETAXEL
Issue Date
201408
Publisher
SPRINGER/PLENUM PUBLISHERS
Citation
PHARMACEUTICAL RESEARCH, v.31, no.8, pp.1978 - 1988
Abstract
To investigate whether delivery of a histone deacetylase inhibitor, vorinostat (VOR), by using solid lipid nanoparticles (SLNs) enhanced its bioavailability and effects on multidrug-resistant cancer cells. VOR-loaded SLNs (VOR-SLNs) were prepared by hot homogenization using an emulsification-sonication technique, and the formulation parameters were optimized. The cytotoxicity of the optimized formulation was evaluated in cancer cell lines (MCF-7, A549, and MDA-MB-231), and pharmacokinetic parameters were examined following oral and intravenous (IV) administration to rats. VOR-SLNs were spherical, with a narrowly distributed average size of similar to 100 nm, and were physically stable for 3 months. Drug release showed a typical bi-phasic pattern in vitro, and was independent of pH. VOR-SLNs were more cytotoxic than the free drug in both sensitive (MCF-7 and A549) and resistant (MDA-MB-231) cancer cells. Importantly, SLN formulations showed prominent cytotoxicity in MDA-MB-231 cells at low doses, suggesting an ability to effectively counter the P-glycoprotein-related drug efflux pumps. Pharmacokinetic studies clearly demonstrated that VOR-SLNs markedly improved VOR plasma circulation time and decreased its elimination rate constant. The areas under the VOR concentration-time curve produced by oral and IV administration of VOR-SLNs were significantly greater than those produced by free drug administration. These in vivo results clearly highlighted the remarkable potential of SLNs to augment the bioavailability of VOR. VOR-SLNs successfully enhanced the oral bioavailability, circulation half-life, and chemotherapeutic potential of VOR.
URI
http://hdl.handle.net/YU.REPOSITORY/31340http://dx.doi.org/10.1007/s11095-014-1300-z
ISSN
0724-8741
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약학대학 > 약학부 > Articles
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