In vivo efficacy of an intratumorally injected in situ-forming doxorubicin/poly(ethylene glycol)-b-polycaprolactone diblock copolymer.
Biomaterials
; 32(20): 4556-64, 2011 Jul.
Article
en En
| MEDLINE
| ID: mdl-21440935
ABSTRACT
The effectiveness of systemically administered anticancer treatments is limited by difficulties in achieving therapeutic doses within tumors, a problem that is complicated by dose-limiting side effects to normal tissue. This work examined injectable in situ-forming gels as a localized drug-delivery system. An MPEG-PCL (MP) solution containing doxorubicin (Dox) existed in an emulsion-sol state at room temperature and rapidly gelled in vitro and in vivo at body temperature. The release of Dox from Dox-loaded MP gels was sustained in vitro over 20 days after an initial burst, indicating that the MP gel acted as a drug depot. Dox-loaded MP gels exhibited remarkable in vitro anti-proliferative activities against B16F10 cancer cells. In vivo experiments employing B16F10 cancer cell xenograft-bearing mice showed that a single intratumoral injection of Dox-loaded MP gel inhibited the growth of tumors as effectively as repeated injections of free Dox, and more effectively than a single dose of free Dox, or saline or gel alone. Consistent with the observed suppression of tumor growth, intratumorally injected free Dox or Dox released from Dox-loaded MP gels caused apoptosis of tumor cells. The tumor biodistribution of free Dox after 1 day was â¼90%, which dropped to â¼15% after 4 days. The biodistribution of Dox following a single injection of Dox-loaded MP gel was also â¼90% on day 1, but remained at â¼13%, even after 15 days. Only a small amount of Dox was found in other organ tissues following intratumoral injection, implying fewer off-target side effects.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Poliésteres
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Polietilenglicoles
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Polímeros
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Doxorrubicina
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Geles
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Antibióticos Antineoplásicos
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Neoplasias
Tipo de estudio:
Evaluation_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Biomaterials
Año:
2011
Tipo del documento:
Article