Development of pluronic micelle-encapsulated doxorubicin and formaldehyde-releasing prodrugs for localized anticancer chemotherapy

Michal Ugarenko, Chee K. Chan, Abraham Nudelman, Ada Rephaeli, Suzanne M. Cutts, Don R. Phillips

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The chemotherapeutic agent doxorubicin forms drug-DNA adducts that are enhanced by formaldehyde-releasing prodrugs such as AN-9. One of the major limitations of doxorubicin is dose-limiting cardiotoxicity; therefore, the use of a targeting strategy that enables drug delivery and release at tumor sites is of great interest. The major aim of this study was to use the Pluronic-ultrasound delivery system to encapsulate doxorubicin and formaldehyde-releasing prodrugs within Pluronic micelles, and then use ultrasound to trigger controlled drug release from micelles. Pluronic micelles themselves were not stable upon dilution and required the use of a stabilizing agent DSPE-PEG2000 to form stable "mixed micelles." Following the separation of free doxorubicin, approximately 60% of doxorubicin remained encapsulated within mixed micelles with a retention half-life of approximately 12 h. The formaldehyde-releasing prodrugs, however, were not retained within mixed micelles, but could potentially be administered separately to doxorubicin-loaded micelles to achieve tumor-localized formation of doxorubicin-DNA adducts. The use of low-frequency, high-power ultrasound (20 kHz, 100 W/cm2) released 7-10% of doxorubicin from mixed micelles. Collectively, these results indicate that the Pluronic-ultrasound system could be used to deliver and release doxorubicin with the potential of forming cytotoxic DNA adducts at tumor sites with coadministrated formaldehyde-releasing prodrugs.

Original languageEnglish
Pages (from-to)283-299
Number of pages17
JournalOncology Research
Volume17
Issue number7
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Poloxamer
Prodrugs
Micelles
Doxorubicin
Formaldehyde
Drug Therapy
DNA Adducts
Neoplasms
Excipients
Half-Life

Keywords

  • AN-9
  • Doxorubicin
  • Formaldehyde
  • Pluronics
  • Ultrasound

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Development of pluronic micelle-encapsulated doxorubicin and formaldehyde-releasing prodrugs for localized anticancer chemotherapy. / Ugarenko, Michal; Chan, Chee K.; Nudelman, Abraham; Rephaeli, Ada; Cutts, Suzanne M.; Phillips, Don R.

In: Oncology Research, Vol. 17, No. 7, 2009, p. 283-299.

Research output: Contribution to journalArticle

Ugarenko, Michal ; Chan, Chee K. ; Nudelman, Abraham ; Rephaeli, Ada ; Cutts, Suzanne M. ; Phillips, Don R. / Development of pluronic micelle-encapsulated doxorubicin and formaldehyde-releasing prodrugs for localized anticancer chemotherapy. In: Oncology Research. 2009 ; Vol. 17, No. 7. pp. 283-299.
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