Development of Vorinostat-Loaded Solid Lipid Nanoparticles to Enhance Pharmacokinetics and Efficacy against Multidrug-Resistant Cancer Cells
- Authors
- Tuan Hiep Tran; Ramasamy, Thiruganesh; Duy Hieu Truong; Shin, Beom Soo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh
- Issue Date
- Aug-2014
- Publisher
- SPRINGER/PLENUM PUBLISHERS
- Keywords
- Bioavailability; Drug resistance; Pharmacokinetics; Solid lipid nanoparticle; Vorinostat
- Citation
- PHARMACEUTICAL RESEARCH, v.31, no.8, pp.1978 - 1988
- Indexed
- SCIE
SCOPUS
- Journal Title
- PHARMACEUTICAL RESEARCH
- Volume
- 31
- Number
- 8
- Start Page
- 1978
- End Page
- 1988
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/22336
- DOI
- 10.1007/s11095-014-1300-z
- ISSN
- 0724-8741
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - COLLEGE OF PHARMACY > DEPARTMENT OF PHARMACY > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/22336)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.