Abstract
Abstract After injection into blood stream an artificial nanoemulsion (NEm) that mimics LDL composition binds to LDL receptors and concentrates in tumor tissues that show LDL receptor overexpression. NEm has been used as carrier to target drugs against neoplastic tissues and was shown to diminish toxicity while increase tumoral inhibition growth in murine models, showing more effective and selectiveness. Daunorrubicin (DNR) is an anthracycline antibiotic that possesses broad spectrum antineoplastic activity, and is one of the most important anticancer agents in use. However, clinical utility is hampered by cumulative, dose limiting cardiotoxicity, myelosupression, and the development of drug resistence. Derivative form of daunorubicin oleate (ODNR) was synthesized and associated to NEM by prolonged ultrassonication and ultracentrifugation Antitumor activity of NEM-ODNR were tested in B16F10 melanoma bearing mice and compared with commercial formulation (DNR) and control group (saline). Tumor growth, presence of metastatic nodes and hematological profile were evaluated. The cytotoxicity of NEm-ODNR was diminished by five times compared to DNR. In dose acute toxicity studies the NEm-ODNR tolerability was 72-times higher compared to commercial DNR. The tumor growth inhibition rate for NEM-ODNR was over 35% when compared to DNR and 59% compared to saline (p < 0,001). There was a significant reduction in animals bearing metastasis for NEM associated treated group (30%) in comparison to the commercial treated (80%). In control group all animals developed metastatic tumors. Hematological profile showed that NEM-ODNR treatment had a 15% raise for red blood cells, compared to 29% of reduction for DNR, 25% of reduction to white blood cells compared to 55% for DNR and 45% reduction of platelets compared to 57% for DNR. Flow cytometry suggested greater antitumor activity for NEm-ODNR group showing remarkable arrest (47%) on DNA fragmentation phase of cell cycle compared to 26% to DNR. Those tests are essential for evaluating the NEM-ODNR formulation and its implementation of future clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2656.
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