Summary
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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| Web resources: | https://cordis.europa.eu/project/id/101149745 |
| Start date: | 01-01-2025 |
| End date: | 31-12-2026 |
| Total budget - Public funding: | - 172 750,00 Euro |
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Original description
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.Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
22-11-2024
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