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Dual Stimuli-Responsive Nanoparticles to Achieve Brain Multi-drugs Delivery Improving the Treatment of Neurodegenerative Disorders

Objective

Leading to disability and morbidity, neurodegenerative disorders (NDs) have a profound socio-economic impact. Given the aging of the population, they are raising remarkable concerns. Several active compounds for NDs treatment showed promising results in-vitro but failed in-vivo due to unfavorable biodistribution and limited biocompatibility. The nanocarriers (NC) proposed in the last decade have certainly improved brain delivery of active compounds, however, the limited bioavailability of the drug and biocompatibility issues make NDs treatment still a hot topic in neuroscience. With BRAVERY, I aim to achieve the spatiotemporal controlled drug release improving the bioavailability of neuroactive compounds in the brain without causing neurotoxicity. To do so, I propose to develop a novel biocompatible multi-drug NC capable of efficiently targeting the brain and releasing the loaded drugs in a controlled manner in response to specific stimuli, after intranasal administration. The proposed NC has three fundamental features: 1) It is mucoadhesive; 2) It degrades in response to two specific stimuli that allow achieving a spatiotemporally controlled release of the carried drugs in the brain; 3) Both NC and products of its degradation are biocompatible, thus limiting neurotoxicity. The biocompatibility and biodistribution of the NC will be evaluated by in-vitro, in-vivo, and ex-vivo analysis. As a proof of concept, the carrier will be loaded with active compounds and the biological effect observed will be compared with the one achieved by the free drugs. The project could have an immediate impact on NDs treatment improving the biological efficacy of the anti-prion protein drug used in this project as model drug. Such a versatile biocompatible multi-drug NC will pave the way toward a new era of NDs treatments, with a remarkable impact on society and health care systems worldwide.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

ISTITUTO DI RICERCHE FARMACOLOGICHE MARIO NEGRI
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 172 750,08
Address
VIA MARIO NEGRI 2
20156 MILANO
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Research Organisations
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Total cost

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