Periodic Reporting for period 1 - Bio2Brain (Nose-to-Brain Delivery of Biopharmaceutics for the therapy of central nervous system diseases: A design-based approach for efficient drug delivery systems)
Reporting period: 2021-01-01 to 2022-12-31
The aim of the Bio2Brain network is the development of a research and training programme to train young scientists in innovating novel technologies to deliver biopharmaceuticals efficiently from the nose to the brain. It thereby offers a unique opportunity to 13 early career researchers to develop new paradigms and treatments in neurological diseases. Bio2Brain will create the fundament for the future transfer of the developed technologies for a later clinical development and GMP manufacturing.
Disorders of the central nervous system (CNS) and the spinal cord affect around 165 million Europeans with diseases such as Multiple Sclerosis, Alzheimer’s disease, and Parkinson’s disease. CNS disorders are often associated with high morbidity, significant side effects, severe suffering of the patients and their families, as well as an enormous burden on the social systems.
Therefore, 18 project partners from academia and industry have joined forces to establish the trans-European research network Bio2Brain to investigate efficient administration routes of biopharmaceuticals for the treatment of disorders of the CNS.
The Bio2Brain network combines partners with expertise in chemistry, biology, neurology physics, pharmacy, clinical and translational neuroscience, computational modelling, regulatory affairs as well as nano- and biotechnology. The trans-European research network offers an exceptional training and collaborative environment for the interdisciplinary and intersectoral training of 13 Early Stage Researchers (ESRs).
Disorders of the central nervous system (CNS) and the spinal cord affect around 165 million Europeans with diseases such as Multiple Sclerosis, Alzheimer’s disease, and Parkinson’s disease. CNS disorders are often associated with high morbidity, significant side effects, severe suffering of the patients and their families, as well as an enormous burden on the social systems.
Therefore, 18 project partners from academia and industry have joined forces to establish the trans-European research network Bio2Brain to investigate efficient administration routes of biopharmaceuticals for the treatment of disorders of the CNS.
The Bio2Brain network combines partners with expertise in chemistry, biology, neurology physics, pharmacy, clinical and translational neuroscience, computational modelling, regulatory affairs as well as nano- and biotechnology. The trans-European research network offers an exceptional training and collaborative environment for the interdisciplinary and intersectoral training of 13 Early Stage Researchers (ESRs).
The Bio2Brain consortium successfully hired its 13 PhD candidates. Our partners received many highly qualified applications and we thank everyone for their interest in our project. The ESRs started their work in October and beginning of November 2021. All of them are enrolled in a PhD programme.
The Bio2Brain network offers scientific as well as soft skill training during the course of the project. Within the first project period an ESR kick-off meeting as well as a Summer school were organised.
The Bio2Brain kick-off meeting took place on 25 November 2021. Unfortunately, due to the restrictions imposed by the worldwide COVID19 pandemic the meeting was conducted online.
The main purpose of the meetings was to welcome all 13 ESRs to the project and introduce the whole network. All ESRs gave presentations on their background and research project and enough time was allowed for questions, feedback and comments. The meeting closed with two seminars on Presentation and Communication as well Team Building and Personal Development.
The Bio2Brain Summer School took place on 25 to 28 July 2022 at the Biberach University of Applied Science (HBC) in Biberach, Germany. The ESRs met for the first time in person and spent one week together attending workshops, going on excursions, and presenting their scientific progresses. The meeting included two workshops, one laboratory workshop on “Antibody Engineering and characterization” and a Regulatory & Quality Workshop on “New trends, Technologies & Challenges in (bio)pharmaceutical manufacturing”. There were six very interesting keynote lectures hold by representatives from Biberach University of Applied Science, Vektor Pharma TF GmbH, Boehringer Ingelheim Biopharmaceuticals GmbH, University of Ulm and Regenold GmbH.
Laboratory rotations to scientific and industrial partners are a key element to promote interdisciplinary and intersectoral exchange, knowledge transfer and workplace mobility within Bio2Brain. Each ESR will spend significant time with at least one academic and one non-academic partner. Due to the COVID19 pandemic and travel restrictions, the secondments were put on hold until early 2022. The whole consortium was very excited that secondments could take place again during the last months.
Furthermore, our ESRs attended a few conferences already to gain experiences and knowledge but also to present their work and first results. One example is the 8th congress of the European Academy of Neurology (EAN), that took place from 25 to 28 June in Vienna, Austria.
From the scientific perspective the following achievements have already been made during the first project period:
Polymeric nanogels were obtained using high dilution radical polymerisation. These nanogels were characterised in terms of monomer conversions and chemical yields.
Chitosan and hyaluronic acid have been successfully modified to achieve modified chitosan polymers. The analysis of mucoadhesive action through rheological determination of the synergism parameter and contact angle measurements indicates the enhancement of the mucoadhesion.
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.
The Bio2Brain network offers scientific as well as soft skill training during the course of the project. Within the first project period an ESR kick-off meeting as well as a Summer school were organised.
The Bio2Brain kick-off meeting took place on 25 November 2021. Unfortunately, due to the restrictions imposed by the worldwide COVID19 pandemic the meeting was conducted online.
The main purpose of the meetings was to welcome all 13 ESRs to the project and introduce the whole network. All ESRs gave presentations on their background and research project and enough time was allowed for questions, feedback and comments. The meeting closed with two seminars on Presentation and Communication as well Team Building and Personal Development.
The Bio2Brain Summer School took place on 25 to 28 July 2022 at the Biberach University of Applied Science (HBC) in Biberach, Germany. The ESRs met for the first time in person and spent one week together attending workshops, going on excursions, and presenting their scientific progresses. The meeting included two workshops, one laboratory workshop on “Antibody Engineering and characterization” and a Regulatory & Quality Workshop on “New trends, Technologies & Challenges in (bio)pharmaceutical manufacturing”. There were six very interesting keynote lectures hold by representatives from Biberach University of Applied Science, Vektor Pharma TF GmbH, Boehringer Ingelheim Biopharmaceuticals GmbH, University of Ulm and Regenold GmbH.
Laboratory rotations to scientific and industrial partners are a key element to promote interdisciplinary and intersectoral exchange, knowledge transfer and workplace mobility within Bio2Brain. Each ESR will spend significant time with at least one academic and one non-academic partner. Due to the COVID19 pandemic and travel restrictions, the secondments were put on hold until early 2022. The whole consortium was very excited that secondments could take place again during the last months.
Furthermore, our ESRs attended a few conferences already to gain experiences and knowledge but also to present their work and first results. One example is the 8th congress of the European Academy of Neurology (EAN), that took place from 25 to 28 June in Vienna, Austria.
From the scientific perspective the following achievements have already been made during the first project period:
Polymeric nanogels were obtained using high dilution radical polymerisation. These nanogels were characterised in terms of monomer conversions and chemical yields.
Chitosan and hyaluronic acid have been successfully modified to achieve modified chitosan polymers. The analysis of mucoadhesive action through rheological determination of the synergism parameter and contact angle measurements indicates the enhancement of the mucoadhesion.
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.
The overall scientific aim of Bio2Brain is the development of an innovative intranasal nose to brain (N2B) drug delivery technology based on the design and synthesis of a biomaterial-based novel class of hydrogel in combination with antibody-loaded functional particles, which will be directly applied to the nasal olfactory region.
The mechanisms of the antibody transport from the nasal mucosa to the CNS and their interaction with the mucosa will be analysed to tailor engineered antibodies for an improved and safe N2B delivery. Numerical simulation and modelling of the interface processes will support the scientific aims.
The past and present scientific work on nanotechnology is characterised by a shortfall in technology transfer which decisively depends upon an up-to-date education and training. The strong presence of industrial partners in the Bio2Brain project will contribute to develop entrepreneurship and creativity by enabling the ESRs to experience the challenges encountered when transferring fundamental research to the industrial application. At the same time, new fundamental research will be seeded by the practical problems encountered in the industrial development. The non-academic beneficiaries and associated partners will provide a crucial contribution to the training of the ESRs by exposing them to a highly innovative industrial environment. In that context, the ESRs will learn to communicate and collaborate with industrial partners and how to apply scientific knowledge into industrial practice. This fosters efficient and long-lasting relationships between academia and industry.
The mechanisms of the antibody transport from the nasal mucosa to the CNS and their interaction with the mucosa will be analysed to tailor engineered antibodies for an improved and safe N2B delivery. Numerical simulation and modelling of the interface processes will support the scientific aims.
The past and present scientific work on nanotechnology is characterised by a shortfall in technology transfer which decisively depends upon an up-to-date education and training. The strong presence of industrial partners in the Bio2Brain project will contribute to develop entrepreneurship and creativity by enabling the ESRs to experience the challenges encountered when transferring fundamental research to the industrial application. At the same time, new fundamental research will be seeded by the practical problems encountered in the industrial development. The non-academic beneficiaries and associated partners will provide a crucial contribution to the training of the ESRs by exposing them to a highly innovative industrial environment. In that context, the ESRs will learn to communicate and collaborate with industrial partners and how to apply scientific knowledge into industrial practice. This fosters efficient and long-lasting relationships between academia and industry.