Abstract #3671: Lipidic nanoparticles in combined chemotherapy: In vivo inhibition of melanoma B16F10 growth

Abstract

Introduction and Objective: Lipidic nanoemulsions that resemble low-density lipoprotein (LDL) binds to LDL receptors and after injection into the bloodstream concentrates in neoplastic tissues wherein those receptors are upregulated. Thus the nanoemulsion can be used as vehicle to direct chemotherapeutic agents to malignant tumors. It was shown that the nanoemulsion increases the therapeutic index of carmustine, paclitaxel and etoposide in murine oncologic models. In patients with advanced cancer it pronouncedly decreases the toxicity of those drugs. This study aims to evaluate in melanoma bearing mice the effects of combined chemotherapy of paclitaxel and etoposide both associated with the nanoemulsion. Materials and Methods: Derivative forms of etoposide and paclitaxel were synthesized and associated to the nanoemulsion prepared by prolonged ultrassonication in aqueous medium and ultracentrifugation. B16F10 melanoma tumor-bearing mice were intraperitonially injected with paclitaxel oleate (9 \#956;mol/kg) and etoposide oleate (9 \#956;mol/kg) associated with the nanoemulsion at days 11th, 13th and 15th after the tumor cells inoculation. This group was compared to melanoma-bearing mice injected with equivalent doses of the single drugs associated with the nanoemulsion, combined therapy with the commercial formulations of paclitaxel and etoposide and a control group treated with saline solution. Tumor growth, presence of metastatic nodes, blood cell counts, and histological data from tumor samples from all treatment groups and controls were evaluated. Results: The tumor growth inhibition rate was over 85% in all treatment groups (p < 0,001) compared to controls. However, the group treated with the nanoemulsion drug combination presented tumors with the smallest cellular density, massive production of collagen fibers and reduction of newly formed vessels. This group also had the smaller percentage of animals bearing metastasis (30%) in comparison to the other treatments (p < 0,05). Blood cell counts showed that all treatments reduced characteristical hematopoietic effects of melanoma such as anemia and thrombocytosis (p < 0,001). Conclusion: Combined drug-targeting therapy of paclitaxel and etoposide derivatives associated to a lipidic nanoemulsion inhibited tumor growth with reduced hematological toxicity, and prevented tumor dissemination more effectively than the single therapy with the two drugs and the combination of commercial formulations of paclitaxel and etoposide.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3671.