Journal article
Intratumoral delivery of beta-lapachone via polymer implants for prostate cancer therapy
Clinical cancer research, Vol.15(1), pp.131-139
01/01/2009
DOI: 10.1158/1078-0432.CCR-08-1691
PMCID: PMC2845536
PMID: 19118040
Abstract
beta-Lapachone (ARQ 501, a formulation of beta-lapachone complexed with hydroxypropyl-beta-cyclodextrin) is a novel anticancer agent with selectivity against prostate cancer cells overexpressing the NAD(P)H:quinone oxidoreductase-1 enzyme. Lack of solubility and an efficient drug delivery strategy limits this compound in clinical applications. In this study, we aimed to develop beta-lapachone-containing polymer implants (millirods) for direct implantation into prostate tumors to test the hypothesis that the combination of a tumor-specific anticancer agent with site-specific release of the agent will lead to significant antitumor efficacy. Survival assays in vitro were used to test the killing effect of beta-lapachone in different prostate cancer cells. beta-Lapachone release kinetics from millirods was determined in vitro and in vivo. PC-3 prostate tumor xenografts in athymic nude mice were used for antitumor efficacy studies in vivo. beta-Lapachone killed three different prostate cancer cell lines in an NAD(P)H:quinone oxidoreductase-1-dependent manner. Upon incorporation of solid-state inclusion complexes of beta-lapachone with hydroxypropyl-beta-cyclodextrin into poly(D,L-lactide-co-glycolide) millirods, beta-lapachone release kinetics in vivo showed a burst release of approximately 0.5 mg within 12 hours and a subsequently sustained release of the drug ( approximately 0.4 mg/kg/d) comparable with that observed in vitro. Antitumor efficacy studies showed significant tumor growth inhibition by beta-lapachone millirods compared with controls (P < 0.0001; n = 10 per group). Kaplan-Meier survival curves showed that tumor-bearing mice treated with beta-lapachone millirods survived nearly 2-fold longer than controls, without observable systemic toxicity. Intratumoral delivery of beta-lapachone using polymer millirods showed the promising therapeutic potential for human prostate tumors.
Details
- Title: Subtitle
- Intratumoral delivery of beta-lapachone via polymer implants for prostate cancer therapy
- Creators
- Ying Dong - Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USAShook-Fong ChinElvin BlancoErik A BeyWareef KabbaniXian-Jin XieWilliam G BornmannDavid A BoothmanJinming Gao
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.15(1), pp.131-139
- Publisher
- United States
- DOI
- 10.1158/1078-0432.CCR-08-1691
- PMID
- 19118040
- PMCID
- PMC2845536
- ISSN
- 1078-0432
- eISSN
- 1557-3265
- Grant note
- R01 CA102792-06 / NCI NIH HHS R01 CA90696 / NCI NIH HHS R01 CA090696-04 / NCI NIH HHS R01 CA090696-05 / NCI NIH HHS P30 CA142543 / NCI NIH HHS R01 CA090696-04S1 / NCI NIH HHS R01 CA090696 / NCI NIH HHS R01 CA102792 / NCI NIH HHS
- Language
- English
- Date published
- 01/01/2009
- Academic Unit
- Preventive and Community Dentistry; Biostatistics; Dental Research
- Record Identifier
- 9983917681702771
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