Physico-chemical and toxicological evaluations of betulin and betulinic acid interactions with hydrophilic cyclodextrins

Abstract

Betulin and betulinic acid are pentacyclic triterpens with antitumor activity, especially on melanoma and skin cancer. Considering their low water solubility, studies have been conducted in order to improve this aspect. One possible solution is the preparation of inclusion complexes with semisynthetic cyclodextrins using different methods. The purpose of this study was the evaluation of the stability constants of betulin and betulinic acid complexes with two cyclodextrins: hydroxypropyl-beta-cyclodextrin and randomly methylated-beta-cyclodextrin, using the Higuchi and Connors phase solubility method. Products have been analyzed by scanning electron microscopy and in vitro tests. The presence of cyclodextrins increases water solubility and biological activity without toxic activity.