Planta Med 2009; 75 - PE53
DOI: 10.1055/s-0029-1234614

Toxicological evaluations for betulinic acid in cyclodextrins complexes on in vitro and in vivo melanoma models

CA Dehelean 1, C Soica 1, A Muresan 2, C Tatu 2, Z Aigner 3
  • 1Faculty of Pharmacy, University of Medicine and Pharmacy Victor Babes Timisoara, Eftimie Murgu Square no.2, RO-300041, Timisoara, Romania
  • 2Faculty of Medicine, University of Medicine and Pharmacy Victor Babes Timisoara, Eftimie Murgu Square no.2, RO-300041, Timisoara, Romania
  • 3Faculty of Pharmacy, Institute of Pharmaceutical Technology, University of Szeged, Zrinyi u.9, H-6720, Szeged, Hungary

Vegetal compounds such as pentacyclic triterpenes with lupan skeleton proved and important antitumor activity. From that group betulinic acid (BA) is an effective antitumor agent with an anti-inflammatory effect [1,2]. These aspect lead to the obtaining of new bioavailable formulations for biological administration that could capacitate their properties and solve their low solubility including cyclodextrin complexation [1,2].

The complexes with gamma cyclodextrins, were prepared by kneading method procedure in 1:2 ratios. In vivo models used C57Bl/6J mice, female, 8 weeks old by inoculation of 1×105 B16 cells (mouse melanoma). Cells were suspended in saline solution [3].The cancer promotion was increased by the UVB exposure 5min/day, 2days/week. The skin damages and metastasis evolution were appreciated by SERS (surface-enhanced Raman scattering) technique and histopathological analysis (HE coloration).

Betulinic acid, an important antitumor and selective melanoma compound [1] was tested in vitro on B16 cell culture and on human mesenchimal stem cells from a stock solution, started at 50µg/ml and in vivo at a dosage of 350mg/bw. Complexes activity (inhibition of proliferation) was increased in vitro with over 10% on both type of tests comparing with the single compound and determine a good answer on in vivo application. The tests were confirmed in vivo by vibrational spectroscopy (peak changes) and histology evaluation (metastasis status).

Betulinic acid as antimelanoma agent reduces metastasis and tumor dimension if is administrated before the vertical development of the pathology and increasing of its available fraction on biological medium improve the therapeutic answer.

Acknowledgements for financial support to GRANT PN 2-ID 1257/2007

References: [1] Fulda, S. (2008) Int. J. Mol. Sci. 9:1096–1107.

[2] Dehelean, C. et al. (2008) Rev. Chim. Bucarest 59:887-.890.

[3] Carson, W.E., Walker, M.J. (2002) Tumor models in cancer research, Humana Press, New Jersey.