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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Evaluation in melanoma-bearing mice of an etoposide derivative associated to a cholesterol-rich nanoemulsion

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Author(s):
Lo Prete, Ana C. ; Maria, Durvanei A. ; Rodrigues, Débora G. ; Valduga, Claudete J. ; Ibanez, Olga C. M. ; Maranhão, Raul C. [6]
Total Authors: 6
Document type: Journal article
Source: Journal of Pharmacy and Pharmacology; v. 58, n. 6, p. 801-808, June 2006.
Field of knowledge: Biological Sciences - Immunology
Abstract

A cholesterol-rich nanoemulsion (LDE) may be used as a vehicle to target antineoplastic drugs against cancer cells. The association of an etoposide derivative to LDE is stable and retains the cytotoxic activity of etoposide. We have evaluated the toxicity and antitumoral action of this new preparation in-vivo. Melanoma-bearing mice and control mice were administered LDE-etoposide oleate or commercial etoposide, either with or without radioactive labelling. The maximum tolerated dose (MTD), tissue distribution, plasma decay curves, pharmacokinetic parameters and antitumoral activity were determined. Association to LDE drastically reduced the drug toxicity, since MTD was approximately five-fold greater than in commercial etoposide. LDE-etoposide oleate was concentrated four-fold in the tumour compared with the normal adjacent tissues, was removed faster from plasma in tumour-bearing mice than in controls, and remained in the bloodstream longer than commercial etoposide. The tumour growth inhibition rate and survival were greater in animals treated with LDE-etoposide oleate compared with commercial etoposide. However, increasing the dose from 17 to 85 uM kg-1 did not result in further improvement of the antitumour action. The incorporation of etoposide oleate to LDE resulted in markedly reduced toxicity and superior antitumoral activity. LDE-etoposide oleate is a promising new weapon for cancer treatment. (AU)

FAPESP's process: 99/01229-2 - Use of artificial liproteins in the study of dislipidemias and in cancer treatment
Grantee:Raul Cavalcante Maranhao
Support Opportunities: Research Projects - Thematic Grants