NEUROTARGET · Treatment of traumatic brain injury using dye-loaded polymeric nanoparticles
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-12-01 → 2020-11-30
- EU contribution
- €171,461
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Treatment of traumatic brain injury using dye-loaded polymeric nanoparticles
Traumatic brain injury (TBI) is the number one cause of death and disability in children and young adults. Despite well-known mechanisms of secondary brain damage after TBI effective treatments have not been established yet. Therefore, novel approaches to develop therapeutics which have translational potential are at urgent need. One promising strategy is exploiting nanoparticles (NPs) to deliver the pharmacological substance into the brain in high concentration. However, the blood-brain barrier (BBB) remains very challenging for nanoparticles to cross and therefore their bio-distribution in the brain is a particularly important topic in this field. Obviously, the lack of methods for the direct observation of NPs’ makes it significantly harder to establish brain targeting. Hence, the detection of NPs at the single-particle level with good spatial-temporal resolution is a key approach for the future development of central nervous system (CNS) drug-delivery systems (DDS). The aim of this project was to establish a nanoscale platform able to deliver pharmacologically active substance into the injured brain for the treatment of TBI that has the potential for clinical translation. The project addressed the following questions: 1) To create and optimize an NP-based platform for drug delivery to the brain (WP1), including tracking NP trajectories in healthy and injured brain. 2) To analyse the ability of the NP platform to transport cargo across the BBB (WP2), including establishing a Forster-resonance energy transport (FRET) nanoscale system to track cargo release in healthy and injured brain. 3) To evaluate the effectiveness of targeted treatment after TBI (WP3).
Data: CORDIS, © European Union
Project objective
Traumatic brain injury (TBI) is the number one cause of disability in children and young adults. Despite well-known mechanisms of secondary brain damage after TBI, effective treatments have not been yet established. Consequently, novel strategies to develop therapeutics which have translational potential are urgently required. One of the major obstacles when trying to treat the brain is the inability of drugs to cross the blood-brain barrier (BBB). Therefore, it is of great importance to develop novel strategies of drug delivery to targeted locations across the intact BBB.Poly(lactide-co-glycolide) nanoparticles (PLGA NP) are safe and biodegradable drug carriers. When coated with poloxamer188, they are able to cross the BBB. However, the exact mechanisms of penetration, as well as their route to target cells in the brain are currently unknown. To investigate this, the applicant will combine three cutting-edge technologies: novel extra-bright PLGA NP, in vivo two-photon microscopy and whole body clearing (uDISCO). These techniques in combination allow 3D visualization at the sub-cellular level of how PLGA NP distribute throughout the body, cross the BBB and release their cargo in vivo.These NP will subsequently be used as carriers to deliver multiple neuroprotective compounds with synergistic action into the brain. This technique allows high specificity and potency of therapeutic compounds, while minimizing the risk of side effects.Ultimately, objective of this approach is to create an optimal novel nano-platform for brain-targeted drug-delivery and based on this, to provide an innovative treatment of TBI that has the potential for clinical translation. Furthermore, the project will enable the applicant to gain extensive knowledge in advanced in vivo microscopy and TBI models, techniques that are well established in the host laboratory, thereby giving him the opportunity to become a leader in this novel field of research running his own research unit in the future
Original text from CORDIS.
Participants
- LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN · PlaneggCoordinatorGermany
Links
Data: CORDIS, © European Union