Planta Med 2009; 75 - PE49
DOI: 10.1055/s-0029-1234610

In vivo toxicological evaluations for betulinic acid and ramified cyclodextrins applied on experimental melanoma models

CA Dehelean 1, C Peev 1, C Soica 1, S Cinta-Pinzaru 2, Z Aigner 3
  • 1University of Medicine and Pharmacy Victor Babes Timisoara, Faculty of Pharmacy, Eftimie Murgu Square no.2, RO-300041, Timisoara, Romania
  • 2University Babes-Bolyai Cluj-Napoca, Faculty of Physics, Mihail Kogalniceanu no.1, RO-400084, Cluj-Napoca, Romania
  • 3University of Szeged, Faculty of Pharmacy, Institute of Pharmaceutical Technology, Zrinyi u.9, H-6720, Szeged, Hungary

The preclinical development of bioactive natural products such as betulinic acid is a major objective of anticancer research programs and their biological applications are very important. Pentacyclic triterpenes with lupan skeleton such as betulinic acid (BA), betulin and lupeol are effective and selective antitumor agents [1,2]. The pharmacokinetic data of BA a structure close to betulin in CD-1 mice had been described by a standard two compartment first-order model applicable also in other in vivo evaluations [1,3]. Branched cyclodextrins are important co-participants to formulations that are increasing the hydrosolubilty [2].

The complexes with oktakis-2,6-di-O-pentyl-gamma cyclodextrin were prepared by kneading procedures in 1:2 ratios. In vivo models were on C57BL/6J mice by a photochemical and inoculation method. The photochemical method used 7,12 dimethyl(a)benzanthracene and TPA as skin promoter and the UVB exposure 5min/day. The inoculation consists in application of 106x0,1ml A2058 (metastatic melanoma) cells and the same UVB exposure [2]. The skin damages were appreciated by FT-Raman with nanosilver particles and histology techniques.

Betulinic acid, an antimelanoma compound lead to important results at 300mg/bw and increasing of its hydrosolubility accentuate the antitumor activity. The tests were confirmed by vibrational spectroscopy and histopathological evaluation. Skin evolution after the treatment lead to important signal and peak changes and these aspects could be correlated with HE histological evaluation.

Betulinic acid is an antimelanoma agent that determines the regression of tumor proliferation in most of cases and malignisation to organs like lungs and changes in the spectral bands for skin between 1100 and 1600cm-1.

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-Bucharest 59:887–890.

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