Project Description
The goal of the NANOEAR consortium is to develop novel multifunctional nanoparticles (MFNPs), which are targetable to selected cell populations, biodegradable, traceable in-vivo, and equipped with controlled drug release. With over 44 million EU citizens with hearing loss and 40 000 profoundly deaf who could immediately benefit from a MFNP-based novel drug carrier system and drug coated cochlear implant, the inner ear is a unique target. Inner ear is a clinically vital target, well representing the central nervous system and other difficult-toaccess body sites; it is isolated, multicompartmental with neural, supporting and vascular targets, and relatively immunoprivileged. Measures of function and structural integrity are quantitative, precise, and objective, permitting detection of loss of a single sensory cell. Moreover, the population of profoundly deaf with cochlear implants, and commercial partners concerned with improving the benefits of sensory neuroprostheses through tissue engineering strategies, provide a direct pathway to eventual clinical application of NP-drug complexes produced by this research consortium.
Novel, - and for the first time - multifunctional, highly penetrating delivery vehicles will be created to carry and release drug/gene precisely to targeted tissue sites and selected cells. In this research consortium multifunctional lipolexes, dendrimers, micelles, mesoporous NPs, polymer-protein complexes, nanocapsules and nano-layers have been constructed to test delivery of molecules/drugs/genes. To target the NPs we are screening of seleted tissues of inner ear (receptor, nerve and vascular cells) to find suitable epitopes against which the targeting peptides will be designed. Four EU/FDA approved degradable biomaterials (PLGA, PCL, Chitosan, Silica) will be tested for targeting, coating, toxicity and payload carrying and release capacity. In addition designed lipoplexies, encapsulated by polyethylene glycol (mPEG), impregnated with drugs, and decorated with targeting ligands and signaling molecules (gadolinium) will be assessed for benchmarking purposes. These data will provide the reference for evaluating the efficacy of different novel MFNPs.
This IP consist of 8 different WPs for design, manufacturing, encapsulation, delivery, targeting, kinetics, toxicity, stability, absorption, bioefficacy and tracktability of drugs. These features will all be specifically assessed and significantly enhanced through nanotechnology-based systems. The fabricated NPs will be applicable to wide variety of drugs (e.g. conventional therapeutics, growth factors, proteins, nucleic acids). Five commercial SMEs are partners in this research consortium, each bringing special knowledge and specific market concerns. We also asses the in-vivo trackability so that drug targeting can be visualized in organs with conventional MRI.
As a demonstration milestone this IP will produce a novel human cochlear implant promoting improved cochlear nerve-implant integration. In this novel demonstration the implant will include a MFNP drug reservoir providing continuous drug delivery and MFNP electrode coatings providing targets for nerve growth.
Concerning current status of the program several sets of NPs have been provided by each producer. Also several different coating techniques have been tried and are under progress. The coating is especialy important as different ligands, signaling molecules and markers can be attached to the surface. In incorporation process, for testing purposes, the NPs are equipped with markers allowing to in´dentify them with histological methods. Of particular interest is GFP gene that is used to demonstrate the efficacy for infection rate of the NPs conceringn cell inocculation and entering the nucleus of the cells. Furhtermore we have worked on two plasmids to demonstrate their efficacy for entering the speicfic cells (PC12 cells) vitro and in rat cochlea in vivo. We have established model data sheets for NPs to be tested and model test protocols for toxicity testing and determining the efficacy of infecting the cells.
