Evaluation of Antitumor Activity of Long-Circulating and pH-Sensitive Liposomes Containing Ursolic Acid in Animal Models of Breast Tumor and Gliosarcoma

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Abstract

Background. Ursolic acid (UA) is a triterpene found in different plant species, possessing antitumor activity, which may be a result of its antiangiogenic effect. However, UA has low water solubility, which limits its use because the bioavailability is impaired. To overcome this inconvenience, we developed long-circulating and pH-sensitive liposomes containing ursolic acid (SpHL-UA). We investigated the antiangiogenic effect of free UA and SpHL-UA in murine brain cancer and human breast tumor models by means of determination of the relative tumor volume, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and histopathological analysis. Methods. The animals were treated with dimethyl sulfoxide in 0.9% (w/v) NaCl, free UA, long-circulating and pH-sensitive liposomes without drug (SpHL), or SpHL-UA. The animals were submitted to each treatment by intraperitoneal injection for 5 days. The dose of free UA or SpHL-UA was equal to 23 mg/kg. Results. Tumor growth inhibition was not observed in human breast tumor-bearing animals. For murine gliosarcoma-bearing animals, a slight tumor growth inhibition was observed in the groups treated with free UA or SpHL-UA (9% and 15%, respectively). No significant change in any of the parameters evaluated by DCE-MRI for both experimental models could be observed. Nevertheless, the evaluation of the mean values of magnetic resonance parameters of human breast tumor-bearing animals showed evidence of a possible antiangiogenic effect induced by SpHL-UA. Histopathological analysis did not present significant change for any treatment. Conclusion. SpHL-UA did not show antiangiogenic activity in a gliosarcoma model and seemed to induce an antiangiogenic effect in the human breast tumor model.

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Rocha, T. G. R., Lopes, S. C. D. A., Cassali, G. D., Ferreira, Ê., Veloso, E. S., Leite, E. A., … Tavitian, B. (2016). Evaluation of Antitumor Activity of Long-Circulating and pH-Sensitive Liposomes Containing Ursolic Acid in Animal Models of Breast Tumor and Gliosarcoma. Integrative Cancer Therapies, 15(4), 512–524. https://doi.org/10.1177/1534735416628273

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