| Grant number: | 17/10016-2 |
| Support Opportunities: | Regular Research Grants |
| Start date: | November 01, 2017 |
| End date: | October 31, 2019 |
| Field of knowledge: | Health Sciences - Pharmacy - Pharmaceutical Technology |
| Principal Investigator: | Marlus Chorilli |
| Grantee: | Marlus Chorilli |
| Host Institution: | Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil |
| City of the host institution: | Araraquara |
| Associated researchers: | Maria Palmira Daflon Gremião |
Abstract
Cervical cancer, a malignant tumor that affects the lower part of the uterus, is the third most frequent tumor in women, caused mainly by persistent infection by some oncogenic types of Human Papillomavirus (HPV). Although diagnostic and preventive capacity has evolved in recent decades through HPV vaccines and Pap smears, cervical cancer is still very much a problem in the female population, especially low-income women, who do not have access to these resources. Thus, treatment involves radiotherapy, gynecological surgery and chemotherapy, which cause a series of drawbacks such as the removal of the uterus and ovaries, as well as the side effects with the administration of conventional chemotherapy such as vomiting, nausea and hair loss. Therefore, the search for bioactive molecules to make cervical cancer treatment more functional and clinically feasible becomes necessary. Thereby, the discovery of peptide drugs, such as CTT1, which showed in vitro and in vivo antitumor action by inhibition of matrix metalloproteinases (MMP), an enzyme widely expressed by cervical tumor cells, has been shown to be an interesting strategy for cervical cancer treatment. However, the clinical use of peptides faces many challenges, mainly due to their physicochemical characteristics and low oral bioavailability, which implies administration through the parenteral route, which results in low adherence of patients to the treatment due to the need for repeated injections leading to thrombophlebitis and tissue necrosis. Thus, the strategy of incorporating it into a delivery system for vaginal administration for localized treatment may allow an adequate, safe and effective treatment for cervical cancer, since the vaginal mucosa has several advantages, such as high permeability and high blood supply. Among drug delivery systems, liquid crystal precursor system (LCPS) with mucoadhesive cationic polymer is a valuable strategy for vaginal administration of CTT1 to provide controlled release and peptide vectoring. Therefore, this project aims to develop an LCPS constituted by polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, oleic acid and chitosan dispersion associated to polyethyleneimine for vaginal administration of the CTT1; then to investigate the in vitro and in vivo cytotoxic action of formulations. Ultimately, it is intended to develop a nanostructured release system for potential application in the treatment of cervical cancer. (AU)
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