Periodic Reporting for period 2 - Bio2Brain (Nose-to-Brain Delivery of Biopharmaceutics for the therapy of central nervous system diseases: A design-based approach for efficient drug delivery systems)
Período documentado: 2023-01-01 hasta 2024-12-31
The Bio2Brain network has successfully achieved its aim of developing a comprehensive research and training program designed to train young scientists in innovating novel technologies for the efficient delivery of biopharmaceuticals from the nose to the brain. This initiative provided a unique opportunity for 16 early-career researchers to establish new paradigms and treatments for neurological diseases. Bio2Brain has laid the groundwork for the future transfer of the developed technologies, paving the way for clinical development and GMP manufacturing.
Central nervous system (CNS) disorders and spinal cord diseases affect approximately 165 million Europeans, with conditions such as Multiple Sclerosis, Alzheimer’s disease, and Parkinson’s disease. These disorders are often associated with high morbidity, significant side effects, severe suffering for patients and their families, and a substantial burden on social systems.
To address these challenges, 18 project partners from both academia and industry have collaborated to create the trans-European research network Bio2Brain, focusing on investigating efficient administration routes for biopharmaceuticals aimed at treating CNS disorders.
The Bio2Brain network successfully combined expertise in chemistry, biology, neurology, physics, pharmacy, clinical and translational neuroscience, computational modelling, regulatory affairs, and nano- and biotechnology. This trans-European research network offered an exceptional training and collaborative environment for the interdisciplinary and intersectoral development of the 16 early-stage Researchers (ESRs).
Central nervous system (CNS) disorders and spinal cord diseases affect approximately 165 million Europeans, with conditions such as Multiple Sclerosis, Alzheimer’s disease, and Parkinson’s disease. These disorders are often associated with high morbidity, significant side effects, severe suffering for patients and their families, and a substantial burden on social systems.
To address these challenges, 18 project partners from both academia and industry have collaborated to create the trans-European research network Bio2Brain, focusing on investigating efficient administration routes for biopharmaceuticals aimed at treating CNS disorders.
The Bio2Brain network successfully combined expertise in chemistry, biology, neurology, physics, pharmacy, clinical and translational neuroscience, computational modelling, regulatory affairs, and nano- and biotechnology. This trans-European research network offered an exceptional training and collaborative environment for the interdisciplinary and intersectoral development of the 16 early-stage Researchers (ESRs).
The Bio2Brain consortium successfully hired 16 early-stage researcher (ESR) candidates, 14 ESRs were enrolled in a doctoral programme. 13 ESRs started their work in October 2021 and beginning of November 2021. All of them were enrolled in a PhD programme. 3 new ESRs joined the network in the beginning of 2024, replacing 3 former ESRs who decided to leave the consortium. The consortium was able to form a strong network with exceptional collaboration opportunities for young scientists. Laboratory rotations to scientific and industrial partners were a key element to promote interdisciplinary and intersectoral exchange, knowledge transfer and workplace mobility within Bio2Brain. Each ESR spent significant time with at least two other partners. In sum, 37 secondments were conducted and the ESRs highly benefitted from their time in other labs, both scientifically and personally.
In addition, the Bio2Brain network offered scientific as well as soft skill training during the course of the project. In sum, 3 summer and 3 winter schools were organised, each hosted by different partners of the consortium. In total, 21 workshops were conducted, covering scientific trainings such as spray drying and synthesis and characterisation of nanomaterials and soft-skill trainings such as time management and scientific writing.
Furthermore, the Bio2Brain ESRs attended a couple of conferences presenting their work and first results. Most importantly, the Bio2Brain consortium hosted a special session at the NANOTEXNOLOGY conference 2024 in Thessaloniki, the International Conference on Nanoscience & Nanotechnologies. 4 PIs supported the 11 ESRs who showcased the latest advancements in their specific projects and collaborative research efforts, ranging from particle-based formulations for intranasal delivery of biopharmaceuticals to advanced imaging techniques for understanding the mechanisms of release and transport of biopharmaceuticals, as well as the rational design of a panel of antibodies. The presentations were very well received by the audience. The subsequent discussions were intensive and lively, which indicated a high level of interest in the topics presented. Additionally, research outcomes and secondment reports were regularly shared on the B2B website and LinkedIn channel. So far, 7 peer-reviewed publications were published and many more submitted.
From the scientific perspective the following achievements have already been made during the project duration:
Various production methods related to delivery systems, including nanoparticles, microparticles, and nanogels, have been developed. Polymeric nanogels as drug carriers were obtained using high dilution radical polymerisation. Particle formulations using the spray-drying method have been implemented. Chitosan and hyaluronic acid have been successfully modified to achieve modified chitosan polymers. Various model drugs have been effectively studied concerning their loading and release from the chosen drug carrier. The final results indicate that the engineered nanobodies exhibit high thermal stability and solubility, facilitating their potential use in therapeutic applications. This underscores the importance of optimizing binding properties for enhanced drug delivery and patient safety. Future studies will focus on in vivo testing to evaluate the safety profiles of these engineered antibodies.
In order to control the safe transport of antibodies in the Regio olfactoria, permeation studies were performed to find out more about the kinetics of the transport. Mathematical sub-models are being integrated following a process system approach with the intent to be solved in order to calculate the drug transfer rate to the mucosa interface. A Safe-by-Design approach was performed by means of data-based modelling.
Toxicity and the precise processes occurring in the brain were identified as potential shared fields of interest in the final project meeting.
In addition, the Bio2Brain network offered scientific as well as soft skill training during the course of the project. In sum, 3 summer and 3 winter schools were organised, each hosted by different partners of the consortium. In total, 21 workshops were conducted, covering scientific trainings such as spray drying and synthesis and characterisation of nanomaterials and soft-skill trainings such as time management and scientific writing.
Furthermore, the Bio2Brain ESRs attended a couple of conferences presenting their work and first results. Most importantly, the Bio2Brain consortium hosted a special session at the NANOTEXNOLOGY conference 2024 in Thessaloniki, the International Conference on Nanoscience & Nanotechnologies. 4 PIs supported the 11 ESRs who showcased the latest advancements in their specific projects and collaborative research efforts, ranging from particle-based formulations for intranasal delivery of biopharmaceuticals to advanced imaging techniques for understanding the mechanisms of release and transport of biopharmaceuticals, as well as the rational design of a panel of antibodies. The presentations were very well received by the audience. The subsequent discussions were intensive and lively, which indicated a high level of interest in the topics presented. Additionally, research outcomes and secondment reports were regularly shared on the B2B website and LinkedIn channel. So far, 7 peer-reviewed publications were published and many more submitted.
From the scientific perspective the following achievements have already been made during the project duration:
Various production methods related to delivery systems, including nanoparticles, microparticles, and nanogels, have been developed. Polymeric nanogels as drug carriers were obtained using high dilution radical polymerisation. Particle formulations using the spray-drying method have been implemented. Chitosan and hyaluronic acid have been successfully modified to achieve modified chitosan polymers. Various model drugs have been effectively studied concerning their loading and release from the chosen drug carrier. The final results indicate that the engineered nanobodies exhibit high thermal stability and solubility, facilitating their potential use in therapeutic applications. This underscores the importance of optimizing binding properties for enhanced drug delivery and patient safety. Future studies will focus on in vivo testing to evaluate the safety profiles of these engineered antibodies.
In order to control the safe transport of antibodies in the Regio olfactoria, permeation studies were performed to find out more about the kinetics of the transport. Mathematical sub-models are being integrated following a process system approach with the intent to be solved in order to calculate the drug transfer rate to the mucosa interface. A Safe-by-Design approach was performed by means of data-based modelling.
Toxicity and the precise processes occurring in the brain were identified as potential shared fields of interest in the final project meeting.
The overall scientific aim of Bio2Brain has successfully been achieved through the development of an innovative intranasal nose-to-brain (N2B) drug delivery technology. This was realized by designing and synthesizing a biomaterial-based novel class of hydrogel in combination with antibody-loaded functional particles, directly applied to the nasal olfactory region. The project thoroughly analyzed the mechanisms of antibody transport from the nasal mucosa to the central nervous system (CNS) and their interactions with the mucosa, leading to the creation of engineered antibodies for improved and safe N2B delivery. Numerical simulations and modelling of interface processes effectively supported these scientific objectives.
The project addressed the historical challenges in technology transfer within the field of nanotechnology, emphasizing the importance of contemporary education and training. The strong involvement of industrial partners in the Bio2Brain project significantly enhanced entrepreneurship and creativity, allowing early-stage researchers (ESRs) to navigate the challenges of translating fundamental research into industrial applications. Furthermore, new foundational research emerged from the practical problems encountered during industrial development. Non-academic beneficiaries and associated partners played a crucial role in training the ESRs by immersing them in a highly innovative industrial environment. Throughout this process, the ESRs learned essential skills in communication and collaboration with industrial partners, effectively applying scientific knowledge to industrial practice. This successful collaboration fostered efficient and sustainable relationships and translation of results between academia and industry.
The project addressed the historical challenges in technology transfer within the field of nanotechnology, emphasizing the importance of contemporary education and training. The strong involvement of industrial partners in the Bio2Brain project significantly enhanced entrepreneurship and creativity, allowing early-stage researchers (ESRs) to navigate the challenges of translating fundamental research into industrial applications. Furthermore, new foundational research emerged from the practical problems encountered during industrial development. Non-academic beneficiaries and associated partners played a crucial role in training the ESRs by immersing them in a highly innovative industrial environment. Throughout this process, the ESRs learned essential skills in communication and collaboration with industrial partners, effectively applying scientific knowledge to industrial practice. This successful collaboration fostered efficient and sustainable relationships and translation of results between academia and industry.