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Danielle Cristinne Azevedo Feio,1 Nayara Cristina Lima de Oliveira,1 Edmundo Luis Rodrigues Pereira,1 Aleksandra Tiemi Morikawa,2 José Augusto Pereira Carneiro Muniz,3 Raquel Carvalho Montenegro,1 Ana Paula Negreiros Nunes Alves,4 Patrícia Danielle Lima de Lima,5 Raul Cavalcante Maranhão,2 Rommel Rodríguez Burbano1 1Human Cytogenetics Laboratory, Institute of Biological Sciences, Federal University of Pará, Belem, 2Heart Institute, University of Sao Paulo Medical School Hospital, Sao Paulo, 3Evandro Chagas Institute, Primate National Center, Ananindeua, 4Department of Clinical Dentistry, Health Sciences Center, Federal University of Ceará, Fortaleza, 5Molecular Biology Laboratory, Post Graduate Program of Amazon Parasitic Biology, Biological and Health Sciences Center, State University of Pará, Belem, Brazil Abstract: Lipid-based nanoparticle systems have been used as vehicles for chemotherapeutic agents in experimental cancer treatments. Those systems have generally been credited with attenuating the severe toxicity of chemotherapeutic agents. This study aimed to investigate the effects of associating paclitaxel (PTX) with a lipid-based nanoparticle system on a nonhuman primate, Cebus apella, documenting the toxicity as measured by serum biochemistry, which is a detailed analysis of blood and tissue. Eighteen C. apella were studied: three animals were treated with cholesterol-rich nanoemulsion (LDE) only, without PTX, administered intravenously every 3 weeks, during six treatment cycles; six animals were treated with PTX associated with LDE at the same administration scheme, three with lower (175 mg/m2) and three with higher (250 mg/m2) PTX doses; and six animals were treated with commercial PTX, three with the lower and three with the higher doses. In the LDE-PTX group, no clinical toxicity appeared, and the weight–food consumption curve was similar to that of the controls. Two animals treated with commercial PTX presented weight loss, nausea and vomiting, diarrhea, skin flaking, 70% loss of body hair, and decreased physical activity. The use of LDE as a carrier at both lower and higher doses reduced the toxicity of the drug in this species, which is closely related to human subjects. This was observed not only by clinical, biochemical, and hematological profiles but also by the histopathological analysis. The results of this study support the assumption that lipid-based nanoparticle systems used as drug carriers can serve as valuable tools to decrease the toxicity and increase the safety of chemotherapeutic agents. Keywords: nanoparticles, LDE, paclitaxel, toxicity, Cebus apella

The immune response modifier Canova® is a homeopathic remedy indicated for patients with depressed immune system, since this drug appears to increase adaptive immunity and induce an immune response against multiple and severe pathological conditions, including cancer. We evaluated the pattern of immune cellular response in non-human primates of the species Cebus apella exposed to N-methyl-N-nitrosourea (MNU) with and without Canova®. Twelve animals were divided into four groups, with three animals each: negative control and three experimental groups, MNU-alone (35 days); MNU (35 days)-plus-Canova® (3 days) and Canova®-alone (3 days). The animals received MNU orally and Canova® by three intravenous injections. Evaluation of the cellular immune response was performed by immunophenotyping of T-lymphocytes (CD4(+), CD8(+)), B-lymphocytes and natural killer cells. Analysis was also performed of the cell cycle. Our results suggest an increase of T-lymphocytes (CD4(+)CD3(+)) only in the Canova® group, while in the MNU-plus-Canova® group only B-lymphocytes increased., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)