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Multifunctional nanoparticles for siRNA release for the treatment of dermal diseases: in vitro and in vivo studies of induced Psoriasis

Grant number: 19/27801-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2020
Effective date (End): February 29, 2024
Field of knowledge:Interdisciplinary Subjects
Principal researcher:Marcio José Tiera
Grantee:André Miguel Martinez Junior
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

This project aims to develop multifunctional nanoparticles seeking the treatment of skin diseases and is based on previous studies. In this study will be used polymeric nanoparticles and hybrid gold-polycation nanoparticles for siRNA release to reduce the expression of cytokines (TNF-alpha and IL-17) associated with the development of Psoriasis, a chronic inflammatory disease that manifests itself in the patients' skin and/or joints and affects up to 3% of the world's population. The composition of chitosan-based polymeric nanocarriers (siRNA), i.e. diisopropylethylamine content (DIPEA) and acetylation, were selected based on in vitro studies using HeLa cells and RAW macrophages, in which was previously evaluated their cytotoxicities and transfections efficiency. Thus, we aim to further improve the efficiency of the vectors obtained by (i) maintaining specific acetylation proportions in chitosan and (ii) associating the polycations with gold nanoparticles (5-20 nm), aiming at increasing the condensation efficiency of siRNA, reducing nanovector dimensions (favoring transdermal transport) and obtaining nanoplatforms responsive to intracellular stimuli. The realization of the project involves the synthesis and physicochemical/biological characterization of polycations and nanovectors, followed by silencing of pro-Psoriasis agents in human epidermis equivalents (3D skin) and in vivo (mice) models of induced Psoriasis by Imiquimod. Its development will be carried out by doctoral student André Miguel Martinez Junior (UNESP - IBILCE), who has been getting experience in the formulation and characterization of non-viral chitosan-based vectors, as well as their in vitro application. The project will have the collaboration of Prof. Antônio Cláudio Tedesco (USP - FFCLRP) and Prof. Vera Aparecida de Oliveira Tiera (IBILCE - UNESP) and will be co-supervised by Prof. Julio Cesar Fernandes (Montréal University - Hôpital du Sacré-CSur, Canada), whose teams will assist in 3D skin and in vivo transfection studies. (AU)

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