Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors.
Cancer Res
; 62(23): 6831-6, 2002 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-12460895
ABSTRACT
Tumor vessels possess unique physiological features that might be exploited for improving drug delivery. In the present study, we investigate the possibility of modifying polyethylene glycol-ylated liposome cationic charge of polyethylene glycol coated liposomes to optimize delivery to tumor vessels using biodistribution studies and intravital microscopy. The majority of liposomes accumulated in the liver, and increasing charge resulted in lower retention in the spleen and blood. Although overall tumor uptake was not affected by charge in the biodistribution studies, intravital microscopy showed that increasing the charge content from 10 to 50 mol % doubled the accumulation of liposomes in tumor vessels, suggesting a change in intratumor distribution; no significant effect of charge on interstitial accumulation could be detected, possibly attributable to spatial heterogeneity. Increased vascular accumulation of cationic liposomes was similar in two different tumor types and sites. Our results suggest that optimizing physicochemical properties of liposomes that exploit physiological features of tumors and control the intratumor distribution of these drug carriers should improve vascular-specific delivery.
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Banco de datos:
MEDLINE
Asunto principal:
Polietilenglicoles
/
Adenocarcinoma
/
Neoplasias del Colon
/
Lípidos
/
Liposomas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Año:
2002
Tipo del documento:
Article
País de afiliación:
Estados Unidos