title: Evaluation of Antitumor Activity of Long-Circulating and pH-Sensitive Liposomes Containing Ursolic Acid in Animal Models of Breast Tumor and Gliosarcoma.
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.
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Talita Guieiro Ribeiro
authors.initials: TG
authors.lastname: Rocha
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Sávia Caldeira de Araújo
authors.initials: SC
authors.lastname: Lopes
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Geovani Dantas
authors.initials: GD
authors.lastname: Cassali
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ênio
authors.initials: Ê
authors.lastname: Ferreira
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Emerson Soares
authors.initials: ES
authors.lastname: Veloso
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Elaine Amaral
authors.initials: EA
authors.lastname: Leite
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fernão Castro
authors.initials: FC
authors.lastname: Braga
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Lucas Antônio Miranda
authors.initials: LA
authors.lastname: Ferreira
authors.affiliation: INSERM U970 , Université Paris Descartes, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Balvay
authors.affiliation: INSERM U970 , Université Paris Descartes, France.
authors.forename: Anikitos
authors.initials: A
authors.lastname: Garofalakis
authors.affiliation: Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil itabra2001@yahoo.com.br.
authors.forename: Mônica Cristina
authors.initials: MC
authors.lastname: Oliveira
authors.affiliation: INSERM U970 , Université Paris Descartes, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Tavitian
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D018316:Gliosarcoma / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000008:administration & dosage*; D061986:MCF-7 Cells; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D014315:Triterpenes; D000097245:Ursolic Acid
keywords: antiangiogenic; dynamic contrast-enhanced magnetic resonance imaging; human breast tumor; long-circulating and pH-sensitive liposomes; murine brain cancer; ursolic acid