Molecular engineering of natural polymers towards ocular gene delivery

• Grant number: 22/06258-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2023
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Fernando Carlos Giacomelli
• Grantee: Fernando Augusto de Oliveira
• Supervisor: Maria Vamvakaki
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Institution abroad: University of Crete, Heraklion (UoC), Greece
• Associated to the scholarship: 19/12944-0 - Structural and biological evaluations of polyplexes obtained by the complexation of DNA and polyethylenimine derivatives containing alkyl chains and lactose towards the treatment of genetic eye disorders, BP.DR

Abstract

This proposal is inserted in the activities embraced by the NanoPol project which has been approved in Europe and receives funding from the European Union's Horizon 2020 research and innovation program under the Marie SkBodowska-Curie Actions (MSCA) Research and Innovation Staff Exchange (RISE) H2020-MSCA-RISE-2018 (Grant Agreement No 823883). The UFABC is one of the Partner Institutions as sponsored by FAPESP thought the Grant No 2019/20470-8. The main objective of the NanoPol project is the creation of new knowledge in the field of polymeric drug delivery systems for ophthalmological applications via an international research network. We particularly target the development of novel non-viral vectors for gene therapies focused on ocular diseases. In this framework, the herein proposed activities are highly complementary to the activities of the PhD candidate in Brazil through the Grant No 2019/12944-0. The BEPE proposal to be conducted at the University of Crete essentially aims the synthesis of natural polymer-based derivatives with potential application in ocular gene delivery. We will focus the synthesis and characterization of a library of poly(2-oxazoline)-grafted chitosan derivatives with further controlled hydrolysis towards the preparation of novel polymeric vectors for gene delivery with tunable properties (particularly, the charge density). Additionally, we propose the evaluation of cationic dextran and chitosan as well as dextran-DNA conjugates in the same framework. The transfection efficiency and cytotoxicity of polymeric gene delivery vectors are usually conflicting properties since commonly higher transfection rates are also linked to higher levels of cytotoxicity. Accordingly, by tuning the charge density of the polymer chains we hypothesize to be able to reach an optimized balance transfection efficiency-cytotoxicity. The number of patients with ocular problems is relevant and the proposed approach may have in the future a societal impact in people's quality of life since it is supposed to contribute to design safer and more effective nanomedicines. (AU)