Nanoparticle delivery across the blood-brain-barrier: Project NAP4DIVE
Published on 08/01/2025 by Christa Ivanova.
Nanoparticle delivery for drug development
Treating diseases that affect the brain and the central nervous system (CNS) in general, is often hindered by the blood-brain-barrier (BBB).
Conditions like Parkinson’s, Alzheimer’s, Schizophrenia and brain cancer affect 180 million Europeans but only less than 5% of current drug candidates can effectively reach the brain.
The BBB is an important mechanism that defends the brain against harmful substances, germs and other things that could cause damage. It is built from a layer of tightly interlocked cells and is a key part of maintaining brain health. This mechanism of protection becomes hindering when substances that are meant to treat the brain cells cannot pass the barrier. This project will focus on nanoparticle delivery throught the BBB to facilitate the development of novel treatment options for brain diseases.
The project in a nutshell
Project NAP4DIVE will develop non-animal alternatives for testing and predicting nanoparticle-based drug delivery across the human BBB. Nanoparticles are used in targeted drug delivery acting as stability enhancers, to increase bioavailability, biodistribution and accumulation of the therapeutics specifically in the targeted area.
Different types of nanoparticles will be tested throughout the project, including but not limited to lipid nanoparticles, polymer nanoparticles and metal-core nanoparticles.
The nanoparticle delivery across the BBB will be studied in laboratory conditions in an in-vitro microfluidic BBB-on-chip model. Organ-on-chip systems are becoming more and more important for the study of cellular processes without the need of using animal models. The European commission strives to advance the development of such systems and models with the aim to reduce animal suffering. In addition, results obtained through animal studies often diverge from results in human studies, making the models less reliable.
NAP4DIVE will revolutionize the traditionally expensive and inefficient drug development process for diseases affecting the CNS by developing two complementary non-animal tools: the aforementioned high-throughput BBB-on-chip and a complementary in silico model based on machine-learning (“NP Design Simulator”), that will help predict the best suited nanoparticles for BBB delivery.
The characterization data will then be gathered in a digital repository and will be made publicly available. The nanoparticle designs which seem to be the most promising will be tested in vitro on the microfluidic BBB-on-chip system, measuring barrier integrity and validated through comparison with clinical and pre-clinical data by the pharmaceutical partner in the consortium.
Microfluidics for nanoparticle delivery
NAP4DIVE relies on an in vitro BBB model for the validation of novel nanoparticle designs before testing them in established animal models. To develop a fully functioning BBB-on-chip system will require the expertise of several project partners, notably Finnadvance (now Akita) and the MIC.
Whereas Finnadvance will focus on the development of the cell culture and the BBB structure for the study of nanoparticle delivery, the MIC will have the responsibility to develop a fluidic system to supplement the cells and to inject the nanoparticle formulations to be tested. For this task, the two companies will work closely with the consortium to determine the best culture and testing conditions.
Conclusion
Establishing novel pathways for the development of safe drug candidates to treat diseases of the CNS will offer new treatment options and addresses one of the most pressing healthcare challenges of the century. In addition to the identification of novel drug candidates, NAP4DIVE will reduce animal use in CNS drug development and lead to an overall reduction of cost. By the end of the 4-year project, market-readiness and cost-effectiveness of the tools will be demonstrated and an extensive ethical assessment will analyze harm- and cost reduction.
This project has received funding from the European Union’s Horizon research and innovation program under HORIZON-HLTH-2024-TOOL-05-two-stage, Grant agreement number 101155875 (NAP4DIVE).
Start date: 1 January 2025
End date: 31 December 2028
EU contribution: € 7 767 276,26