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Environmentally-responsive supramolecular polymeric assemblies for the intracellular delivery of therapeutic DNA: towards a toolbox for novel generation of nanopharmaceuticals in ophthalmology

Abstract

This proposal is inserted in the NanoPol Project which has been approved in Europe and receives funding from the European Union's Horizon 2020 research and innovation programme 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). The main objective of the NanoPol project is the creation of new knowledge in the field of polymeric drug delivery systems for ophthalmological applications. The international research network wishes to design, synthesize and study novel polymer architectures and formulations in this framework. We wish to particular focus, as a Partner Institution, in the development of novel non-viral vectors for gene therapies focused on ocular diseases. It is nowadays well accepted that a number of blinding dystrophies is linked to aberrations in the retina and genetic disorders. Accordingly, gene therapy has been identified as a favored candidate for such treatments however, gene transport into the ocular surface cell is difficult due to several physiological obstacles including the poor corneal permeability. We will evaluate evaluated the potential of surface functionalized polyplexes and stimuli-responsive polymersomes as gene-delivery platforms to human retinal pigment epithelium (RPE) cells. The polymersomes will be produced from novel synthesized pH-responsive PHPMAm-b-PDPAn block copolymers and the polyplexes will be manufactured from hydrophobically and-or sugar-modified polyethyleneimine (PEI). We target more effective cellular uptake of the assemblies and further gene transfection into hard-to-transfect human RPE cells. (AU)

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