Avaliação da atividade antitumoral dos complexos de inclusão de ofloxacino com ciclodextrinas em células de câncer de mama MDA-MB-231

Abstract

The treatment of breast cancer is complex and often limited by its adverse effects, especially when it comes to the subtype that does not express hormone receptors and epidermal growth factor 2. The development of a new drug is expensive and time-consuming, therefore, it is necessary to search for other strategies for the treatment with better cost-effectiveness, such as the repositioning of drugs. Fluoroquinolones are antimicrobials, which have cytotoxic activity in several cancer cell lines reported in studies. Ofloxacin is a second-generation fluoroquinolone, this drug has a broad spectrum of bactericidal action against Gram-negative bacteria and Gram-positive by inhibition of DNA gyrase and topoisomerase IV. However, ofloxacin has low solubility in water, which can hinder its dissolution and bioavailability, therefore, an alternative to improve these aspects is fundamental. One possibility is complexation with cyclodextrins, structures capable of modifying physicochemical characteristics of drugs, including solubility. Thus, the present work sought to evaluate the in vitro immunomodulation of inclusion complexes of ofloxacin with betacyclodextrin (OFLOX/βCD) and 2-hydroxypropyl-β-CD (OFLOX/HPβCD), against the breast MDA-MB- 231. It was possible to observe that the cytotoxicity of the OFLOX/βCD and OFLOX/HPβCD complexes is time and dose dependent. At the highest concentrations (300 μM), the complexes induced apoptosis and necrosis. The OFLOX/HPβCD complex showed better results than the OFLOX/βCD complex.