Development of a nanostructured lipid carrier containing pool of siRNAs associated with the antitumor agent as a multifunctional therapeutic approach for skin Cancer

• Grant number: 19/04448-2
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2019
• Effective date (End): February 28, 2022
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal researcher: Maria Vitória Lopes Badra Bentley
• Grantee: Juliana dos Santos Rosa
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Currently, skin Cancer is one of the most prevalent diseases in the world and one of the most commonly diagnosed malignancies. The main molecular pathways involved in the development of skin Cancer are the Hedgehog (Hh) pathway, which is associated with signs of proliferation, growth and control of cell fate in many tissues via the EGFR receptor, which is associated with cell differentiation to be related to tumorigenesis and the apoptosis pathway, which is common to all types of Cancer. Multifunctional therapies that combine antitumor drugs and other molecules, such as siRNAs, have been widely studied for Cancer treatment, aiming at therapeutic action in different pathways of disease development. Nanostructured Lipid Carriers (CLN) are considered ideal for the topical release of drugs because of their interaction with cutaneous tissue. In this project, a CLN will be developed and optimized by the high pressure homogenization method and preliminary studies will be carried out on the scheduling of the production process of this CLN, for the purpose of production in larger scales (Scaling up). This CLN will have a multifunctional character, containing a pool of specific siRNAs and an antitumor, namely 5-fluorouracil, aiming at a therapy that inhibits the different molecular pathways of skin cancer, thus obtaining a synergistic action, which will culminate in reduction/remission of the skin tumor. It will be characterized in physical and chemical morphological aspects, evaluated in conventional cellular assays of cell viability and transfection, as well as complexation with the siRNAs. In an unpublished form, an alternative animal testing will be performed for permeation and retention tests on human skin using the hOSEC model. Finally, a xenographic animal model will be developed with the purpose of evaluating the antitumor activity of the multifunctional system developed. (AU)

Scientific publications

(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)

LEITE, MARCEL NANI; ROSA VIEGAS, JULIANA SANTOS; GARCIA PRACA, FABIOLA SILVA; DE PAULA, NATALIA APARECIDA; ZAMBELLI RAMALHO, LEANDRA NAIRA; LOPES BADRA BENTLEY, MARIA VITORIA; CIPRIANI FRADE, MARCO ANDREY. Ex vivo model of human skin (hOSEC) for assessing the dermatokinetics of the anti-melanoma drug Dacarbazine. European Journal of Pharmaceutical Sciences, v. 160, MAY 1 2021. Web of Science Citations: 0.

VIEGAS, JULIANA SANTOS ROSA; PRACA, FABIOLA GARCIA; KRAVICZ, MARCELO; BENTLEY, MARIA VITORIA LOPES BADRA. Therapeutic applications and delivery systems for triptolide. DRUG DELIVERY AND TRANSLATIONAL RESEARCH, v. 10, n. 6, SI AUG 2020. Web of Science Citations: 0.

NEVES BORGHETI-CARDOSO, LIVIA; ROSA VIEGAS, JULIANA SANTOS; PUPO SILVESTRINI, ANA VITORIA; CARON, ANGELO LUIS; PRACA, FABIOLA GARCIA; KRAVICZ, MARCELO; LOPES BADRA BENTLEY, MARIA VITORIA. Nanotechnology approaches in the current therapy of skin cancer. Advanced Drug Delivery Reviews, v. 153, n. SI, p. 109-136, JAN 1 2020. Web of Science Citations: 2.