Evaluation of the potential of muco-adhesive liquid-crystalline systems for vaginal administration of curcumin in the treatment of cervical cancer

Author(s)

Francesca Damiani Victorelli

• Document type: Master's Dissertation
• Press: Araraquara. 2020-03-09.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Farmacêuticas. Araraquara
• Defense date: 2020-01-28
• Advisor: Marlus Chorilli; Giovana Calixto

Abstract

Cervical cancer is the gynecological tumor that causes the most deaths in the world among women, representing a major public health problem. Conventional treatments involve gynecological surgery, radiotherapy and radiochemotherapy, which are restricted and have several side effects, negatively impacting patients' quality of life. In view of this scenario, it is extremely important to search for new bioactive molecules for use in antitumor treatment, such as curcumin (CUR), which acts by inducing apoptosis in cancer cells. However, it has low aqueous solubility, which makes its use difficult. To solve this problem, a strategic alternative is its incorporation into liquid crystalline systems (LCSs) and liquid crystalline nanoparticles (LCNPs). These systems have the ability to control drug release, in addition to potentiating their action, resulting in increased concentration in the tumor and reduced damage to normal tissue. The objective of Chapter 1 was to develop SLCs containing ethoxylated 20 and propoxylated 5 cetyl alcohol, oleic acid and aqueous phase containing water (FW) or dispersion of chitosan associated with polyethyleneimine (FPC) for vaginal administration of CUR and to characterize them using microscopy polarized light (MLP), low-angle X-ray scattering (SAXS), rheology, texture profile and mucoadhesion in addition to conducting in vitro release, permeation and retention studies, cytotoxicity assay and checking vascular changes in the chorioallantoic membrane model of chicken embryo (CAM). The objective of Chapter 2 was to develop SLCs containing monoolein, oleic acid and and aqueous phase containing dispersion of chitosan associated with polyethyleneimine and NPLCs consisting of monoolein, DOTAP and poloxamer 127 and to characterize them using low angle X-ray scattering (SAXS), particle size and polydispersity and cryogenic transmission electron microscopy (Cryo-TEM) in addition to conducting in vitro release, permeation and retention studies. The results of MLP and SAXS revealed that the FPC formulation presented lamellar phase, the CH formulation hexagonal phase and the NPLCs cubic phase. The results suggested that NPLCs have a nanoscale scale, since the particles had a diameter between 166.67 to 182.71 nm and PdI in the range of 0.126 to 0.278. The Cryo-TEM of the NPLCs showed that cubosomes were formed. Rheology determined that the formulations FPC and FW showed pseudoplastic and thixotropic behavior and FPC demonstrated better mechanical and mucoadhesive properties, which performance is desirable for topical formulations. The in vitro release, permeation and retention studies showed that the formulation FPC released in 12 hours 7.79%, FW 7.04%, CH 1.82% and NPLCs 42.04% of CUR, acting as delivery systems prolonged. The formulations FW and FPC retain in the vaginal mucosa around 2.3%, CH 1.11% and NPLCs 8.88% CUR. The formulations FW and FPC containing or not CUR showed biocompatibility with L929 cells and toxicity for Hela cells. Finally, it was possible to observe a decrease in the caliber and the number of vessels in the CAM after the application of FPC. Therefore, in view of the results obtained, it can be concluded that the developed systems presented interesting characteristics for the treatment of cervical cancer. (AU)

• FAPESP's process: 17/23357-2 - Potential evaluation of liquid crystal precursors systems for vaginal administration of curcumin in the cervical cancer treatment
• Grantee: Francesca Damiani Victorelli
• Support Opportunities: Scholarships in Brazil - Master