Development of pluronic micelle-encapsulated doxorubicin and formaldehyde-releasing prodrugs for localized anticancer chemotherapy.
Oncol Res
; 17(7): 283-99, 2009.
Article
in En
| MEDLINE
| ID: mdl-19408574
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Prodrugs
/
Doxorubicin
/
Drug Delivery Systems
/
Antibiotics, Antineoplastic
Limits:
Humans
Language:
En
Journal:
Oncol Res
Journal subject:
NEOPLASIAS
Year:
2009
Type:
Article
Affiliation country:
Australia