Potential evaluation of liquid crystal precursors systems for vaginal administration of curcumin in the cervical cancer treatment

Abstract

Cervical cancer is the gynecological tumor that causes most deaths in the world among women, representing a big public health problem. The main symptoms are abnormal vaginal bleeding and pain, being the persistent infection caused by human papillomavirus (HPV), the major factor related to this cancer. Thus, women resort to conventional treatments, such as gynecological surgery, radiotherapy and radiochemotherapy, which are restricted and have several side effects, negatively impacting patients' quality of life. Considering this scenario, it is extremely important to research new bioactive molecules for use in antitumor treatment, such as curcumin (CUR), which acts by inducing apoptosis in cancer cells, promoting activation of caspases and pro-apoptotic proteins and inhibition of antiapoptotic proteins. However, it has low aqueous solubility, which makes its use difficult. In order to solve this problem, a strategic alternative is its incorporation into liquid crystal percursor systems (LCPS) for vaginal administration, since this pathway is extremely useful when a local effect of the drug is desired, avoiding first-pass metabolism. LCPS show the characteristics of liquid crystals, such as the ability to control drug release, and potentiate the drug's action, leading to an increase in its concentration in the tumor and reduction of damage to normal tissue. In this system it is still possible to add polymers such as chitosan (CS) and polyethyleneimine (PEI), which can contribute to the increase of the contact time of the formulation with the vaginal mucus. The aim of this work is to develop LCNs constituted of cetyl alcohol ethoxylated 20 and propoxylated 5, oleic acid and aqueous phase containing polymeric dispersion of CS associated to PEI for vaginal administration of CUR and to characterize them using polarized light microscopy, small-Angle X-ray scattering (SAXS), rheology and mucoadhesion. The in vitro release, permeation and retention tests will be carried out and later, it is intended to investigate the cytotoxic action in vitro and in vivo of the formulations. Thus, it is intended to develop a nanostructured release system for potential application in the treatment of cervical cancer. (AU)