Liquid crystal precursor systems as a strategy for vaginal administration of CTT1 peptide: pharmacotechnical development and potential application for the treatment of cervical cancer

• Grant number: 17/10016-2
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2017 - 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
• 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)

Scientific publications

(7)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VICTORELLI, FRANCESCA DAMIANI; FIORAMONTI CALIXTO, GIOVANA MARIA; DOS SANTOS RAMOS, MATHEUS APARECIDO; BAUAB, TAIS MARIA; CHORILLI, MARLUS. Metronidazole-Loaded Polyethyleneimine and Chitosan-Based Liquid Crystalline System for Treatment of Staphylococcal Skin Infections. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, v. 14, n. 1, p. 227-237, JAN 2018. (14/50928-2, 13/01565-1, 17/10016-2)

DE ARAUJO, PATRICIA ROCHA; FIORAMONTI CALIXTO, GIOVANA MARIA; DA SILVA, ISABEL CRISTIANE; DE PAULA ZAGO, LUCAS HENRIQUE; OSHIRO JUNIOR, JOAO AUGUSTO; PAVAN, FERNANDO ROGERIO; RIBEIRO, ANDERSON ORZARI; FONTANA, CARLA RAQUEL; CHORILLI, MARLUS. Mucoadhesive In Situ Gelling Liquid Crystalline Precursor System to Improve the Vaginal Administration of Drugs. AAPS PHARMSCITECH, v. 20, n. 6, AUG 2019. (17/10016-2)

FONSECA-SANTOS, BRUNO; ARAUJO, GIOVANNA ANGELI; FERREIRA, PAULA SCANAVEZ; VICTORELLI, FRANCESCA DAMIANI; PIRONI, ANDRESSA MARIA; ARAUJO, VICTOR HUGO SOUSA; CARVALHO, SUZANA GONCALVES; CHORILLI, MARLUS. Design and Characterization of Lipid-Surfactant-Based Systems for Enhancing Topical Anti-Inflammatory Activity of Ursolic Acid. PHARMACEUTICS, v. 15, n. 2, p. 14-pg., 2023-02-01. (17/10016-2, 17/22928-6, 17/23357-2, 19/10761-5, 15/05394-2, 16/22544-0)

VICTORELLI, FRANCESCA DAMIANI; DE OLIVEIRA CARDOSO, VALERIA MARIA; FERREIRA, NATALIA NORONHA; FIORAMONTI CALIXTO, GIOVANA MARIA; FONTANA, CARLA RAQUEL; BALTAZAR, FATIMA; DAFLON GREMIAO, MARIA PALMIRA; CHORILLI, MARLUS. Chick embryo chorioallantoic membrane as a suitable in vivo model to evaluate drug delivery systems for cancer treatment: A review. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v. 153, p. 12-pg., 2020-08-01. (17/10016-2, 17/23357-2, 19/07245-5, 13/01565-1, 18/04546-1, 16/06337-5, 15/21412-0, 14/50928-2, 16/09671-3)

VICTORELLI, FRANCESCA DAMIANI; DE OLIVEIRA CARDOSO, VALERIA MARIA; FERREIRA, NATALIA NORONHA; FIORAMONTI CALIXTO, GIOVANA MARIA; FONTANA, CARLA RAQUEL; BALTAZAR, FATIMA; DAFLON GREMIAO, MARIA PALMIRA; CHORILLI, MARLUS. Chick embryo chorioallantoic membrane as a suitable in vivo model to evaluate drug delivery systems for cancer treatment: A review. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v. 153, p. 273-284, AUG 2020. (14/50928-2, 19/07245-5, 18/04546-1, 13/01565-1, 16/09671-3, 15/21412-0, 16/06337-5, 17/10016-2, 17/23357-2)

DA SILVA, PATRICIA BENTO; SOUSA ARAUJO, VICTOR HUGO; FONSECA-SANTOS, BRUNO; SOLCIA, MARIANA CRISTINA; RIBEIRO, CAMILA MARINGOLO; DA SILVA, ISABEL CRISTIANE; ALVES, RENATA CAROLINA; PIRONI, ANDRESSA MARIA; LOPES SILVA, ANA CAROLINA; VICTORELLI, FRANCESCA DAMIANI; et al. Highlights Regarding the Use of Metallic Nanoparticles against Pathogens Considered a Priority by the World Health Organization. Current Medicinal Chemistry, v. 28, n. 10, p. 1906-1956, 2021. (18/00163-0, 17/10016-2, 13/14957-5)

FERREIRA, P. S.; VICTORELLI, F. D.; RODERO, C. F.; FORTUNATO, G. C.; ARAUJO, V. H. S.; FONSECA-SANTOS, B.; BAUAB, T. M.; VAN DIJCK, P.; CHORILLI, M.. p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis. International Journal of Pharmaceutics, v. 603, JUN 15 2021. (19/10261-2, 17/22928-6, 17/10016-2, 18/22658-1)