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Soft Biocompatible Polymeric Nanostructures: A Toolbox for Novel Generation of Nano Pharmaceuticals in Ophthalmology

Periodic Reporting for period 1 - NanoPol (Soft Biocompatible Polymeric Nanostructures: A Toolbox for Novel Generation of Nano Pharmaceuticals in Ophthalmology)

Okres sprawozdawczy: 2019-03-01 do 2022-12-31

We propose a research and innovation project that aims to develop a rational, knowledge-based toolbox for the fabrication of (1) biodegradable and biocompatible associating (gel-forming) polymers, (2) nanogels and (3) nanoparticles tailored as multifunctional therapeutic agents in ophthalmological applications. We seek for novel methods to replace currently used approaches with biocompatible and biodegradable synthetic/natural polymers. Macromolecules of increasingly complex architectures including block, graft and star-like polymers will be explored with respect to their ability to build up transient networks or nanoparticles with well-controlled rheological and structural properties and targeted performance. Profound understanding of the relation between architectural complexity and properties of the macromolecules is crucial for the fabrication of functional polymer-based materials for biomedicine and will greatly enhance the competitiveness of Europe in the field. Such conceptual understanding can only be achieved based on a rational interdisciplinary approach, in which theory and simulations guide experiments. Our work plan includes the design, synthesis and characterization of novel macromolecular architectures dictated by theoretical and simulation outcomes on the properties of the materials, followed by toxicity and in vitro/in vivo testing of the materials/structures and industrial feasibility studies. The macromolecular assemblies will be investigated as complex carriers enabling (1) prolonged retention in the eye and (2) controlled ocular drug release under external stimuli (i.e. temperature, light, pH). The synergy resulting from the cooperation between world-leading in their respective fields academic groups and companies though the effective secondments plan will provide a unique interdisciplinary research and training environment that will allow to address unmet challenges in the area and will ensure European leadership in cutting-edge technologies.
In the first reporting period the project focused on the synthesis and characterization of novel, therapeutically safe and biocompatible polymers (such as polysaccharides, poly(2-oxazoline)s and degradable polyesters) aiming to develop new advanced drug carriers for ocular drug delivery. We have designed, synthesized and characterized novel macromolecular architectures, which will allow us to prepare polymer hydrogels or self-assembled nanostructures to encapsulate and deliver the drugs. The aqueous solution properties of the library of thermo-responsive water-soluble polymers and polymer hydrogels were investigated. This includes linear and star-like homopolymers. Physicochemical characterization using microcalorimetry, dynamic light scattering and UV-Vis spectroscopy was carried out.
Theoretical modelling of the solution properties of molecular brushes with ionically charged side chains and of self-organized solution nanostructures and cross-linked or self-assembled gels formed by amphiphilic graft-copolymers was also performed.
In vitro studies focused on mucoadhesive formulations of pilocarpine and the complexation between ofloxacin as a model ophthalmic drug and gellan gum. Ex vivo approaches to study diffusion and gelation of polymer formulations following injections into the eye were also developed. Finally, liposomal carriers with improved retention on the ocular surface and hydrogels and liposomes for the posterior area of the eye were studies in vivo.
The industrial implementation of the materials and processes is being explored by the industrial project partners and the project results were disseminated in a large number of publications in scientific journals and in conference presentations.
Four Master thesis and two PhD thesis have been completed so far based on the project results. A project website was developed, a Linkedin page for the project has been created, 2 popular articles were published, a video at youtube was produced and the researchers participated at the Researchers Night (2022) to disseminate the project results to the general public.
Biodegradable and biocompatible block- and graft- copolymers are most promising carrier materials for drug delivery applications. In this proposal, we aim to use readily available and purposely synthesized/functionalized temperature- and pH-responsive macromolecules capable of undergoing stimuli-triggered gelation or assembly into nanoparticles. Dendritic or bottle-brush architectures will be selected as drug-bearing modules in certain cases to increase the number of binding cites per macromolecule or per particle (i.e. loading capacity). Chemically cross-linked nanogels covalently linked or co-assembled with one or several types of biologically active molecules will be also investigated to increase the drug loading. Carefully selected drugs representing the most challenging and clinically relevant pharmaceuticals in ocular delivery nowadays will be investigated.
Among the projects’ goals is the design of new and safe (bio)materials that can be produced and commercialized in formulations for controlled ocular drug release. The outputs of the NanoPol project is being exploited following a continuous identification, monitoring and qualification of the obtained results that are either kept confidential to be legally protected (via patents and licenses to ensure intellectual property for instance) and/or transferred to third parties.
The dissemination/communication activities of the project aim to increase the awareness of the public, and in particular the younger people, about the work performed by the network and its social impact. They will also help to attract younger people to scientific careers and improve the profile and image of science to the general public.