Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - N2B-patch (Nose to Brain Delivery of NG-101 via the Olfactory Region for the Regenerative Treatment of Multiple Sclerosis Using Novel Multi-functional Biomaterials Combined with a Medical Device)

Teaser

N2B-patch stands for Nose-to-Brain-patch. We aim to develop an innovative technology for multiple sclerosis (MS) treatment by developing a ‘nose to brain’ (N2B) delivery system which will avoid the need for injections and oral medicine. The long-term objective is to...

Summary

N2B-patch stands for Nose-to-Brain-patch. We aim to develop an innovative technology for multiple sclerosis (MS) treatment by developing a ‘nose to brain’ (N2B) delivery system which will avoid the need for injections and oral medicine. The long-term objective is to improve treatment of MS patients.
The therapy of central nervous system (CNS) diseases like MS is still an unmet medical need due to the low CNS bioavailability of innovative drugs like antibodies. On the other hand, the N2B transport of substances is scientifically well-known and a recently clinically proven alternative route of administration as the so-administered substances can bypass the blood-brain barrier (BBB). Nevertheless until now, highly efficient technologies for olfactory uptake and direct brain delivery are missing.
We aim to develop an innovative N2B drug delivery technology for the treatment of MS based on the synthesis of a biomaterial-based innovative galenic formulation, a novel class of hydrogel matrix-patch and a medical applicator device system. The N2B route of administration provides a minimally invasive method of bypassing the BBB. Moreover, the innovative multifunctional galenic formulation of N2B-patch aims to shield sensitive drugs and maintain the drug’s bioactivity.
The direct transport route from the nasal cavity to the brain, bypassing the BBB, could potentially offer an exciting method for central nervous system drug delivery. It may be used not only for demyelinating disorders such as MS but also for other neurological and neurodegenerative indications or tumours.

N2B-patch aims at the following scientific and technological objectives during a 4-year period:
1. Development of a multifunctional hydrogel matrix with different mechanical and viscoelastic characteristics to achieve the required properties.
2. Development of multifunctional biomaterial-based particles.
3. Proof-of-concept, pharmacokinetics (PK) and efficacy of the API N2B drug transport.
4. Design of the application process.
5. Design and manufacturing of the Container Closure System (CCS).
6. Implementation of scale-up processes related to the galenic formulation.
7. Assessment of regulations and ethics in order to deliver proof of concept and PK data in vivo.
8. Full exploitation of project results along the whole value-chain.
9. Communication and Dissemination activities.

The N2B-patch team will deliver a proof of concept of its therapeutic potential. Science, industry and patients’ representatives work hand in hand in order to achieve the project objectives and maximise impact for patients and their relatives, health professionals and European industries. They are guided by regulatory and business exploitation experts.

Work performed

The project addresses the development of a biomaterial-based galenic formulation in combination with a medical device for the treatment of MS.
The development of the formulation including an ensemble composed of particles and hydrogel started with the beginning of the project. Various particles had been manufactured for further testing. After selection of the lead matrix, the particles will be tailored for the matrix-particle combination. Methods to determine the rheology and stability were established. Novel techniques to evaluate adhesion and spreading were set-up. Different materials are currently screened to verfiy if they achieve the requirements.
The validity of the end product including the applicator and the galenic formulation is a very important step. Therefore, the setting of the user-requirement specifications (URS) started where the product quality related all relevant attributes and their specifications are defined for safe medicinal product development. The application of the hydrogel into the nasal cavity was simulated. Although foreseen at a later stage of this project, the experimental work on the application process has already started to support the screening of an appropriate hydrogel matrix.
From the very beginning of the project certified material for establishment of formulations and manufacturing processes has been used. For the reduction of the later effort that can be caused by use of non-GMP material differing from GMP conformant material quality, the partners achieved sustained quality at lab scale development batches and also mid-scale up-scaling feasibility batches.
Preparatory work for exploitation of project results along the whole value-chain was performed: A targeted survey for patients was prepared and translated in different languages. It will be distributed through the national MS patient’s platforms in different EU countries.
A Communication and Dissemination plan was established,. Besides general communication activities (e.g. logo, website, Flyer, video animation), four peer-reviewed open access publications were accepted. N2B-patch is present in Social Media, e.g. Youtube and LinkedIn.
EMSP, the European Multiple Sclerosis Platform, has provided feedback with the wording of the project material to make it understandable for lay persons (patients) as well as to make sure that the wording tempers unrealistic expectations.
Furthermore, the consortium attended relevant scientific conferences, held presentations or presented posters related to the N2B-patch project, this involves also patient-related events.

Final results

Our project is a brand new approach that aims to develop a delivery technology based on the synthesis of a biomaterial-based innovative galenic formulation, a novel class of hydrogel matrix-patch and a medical applicator device system. Moreover, the innovative multifunctional galenic formulation aims to shield sensitive drugs and maintain the drug’s bioactivity.

The N2B-patch project aims to deliver the following three outputs (for illustration see figure enclosed):
A: An Ensemble composed of biomaterial-based drug particles and an innovative API (biomolecules) for MS treatment.
B: The hydrogel formulation as a minimally-invasive carrier.
C: The applicator device as integral part of the functional and minimally-invasive system.

The N2B-patch project aims to have considerable impacts on society as a whole, on markets and research. The effective treatment of CNS disorders is still an “unmet medical need” connected with high morbidity, significant side effects, suffering of the patients and their families, as well as an enormous burden on the welfare systems.
The N2B-patch project addresses these issues by delivering the following impacts:
• Innovative biomaterials for the treatment of patients with demyelinating disorders of the CNS.
• Reduced direct and indirect costs linked to these diseases and their treatment.
• Enhance competitiveness of the biomaterials and biomedical industries in the EU.
• Dissemination of results.
• A N2B-patch Business case - N2B-patch platform technology.
• Improving the innovation capacity and the integration of new knowledge.
• Strengthening competitiveness and growth by meeting the needs of European and global markets.
• Improving patients ’ quality of life due to minimally invasive action and longer duration of implants and device.
• Sustainability and environmental benefit.

N2B-patch perfectly matches market and user needs in a cost effective and thus competitive manner.

Website & more info

More info: https://n2b-patch.eu/.