The overall aim of N2B-patch is the development of a new innovative N2B drug delivery technology based on the synthesis of a biomaterial-based innovative galenic formulation that will be applied with the aid of a novel medical device equipped with a container closure system (CCS) as a hydrogel patch to the nasal olfactory region for the chronic treatment of MS. The galenic formulation will consist of drug loaded biodegradable polymer particles (e.g., chitosan, polylactic-co-glycolic acid, PLGA) embedded into a biodegradable hydrogel matrix (e.g., hyaluronic acid (HA)-based) to be deposited as a patch onto the olfactory region. A pH-sensitive, mucoadhesive particle coating (e.g., chitosan, chitosan derivatives) will ensure an environment-specific adhesion to the olfactory epithelium. This novel technology will largely enhance the controlled and sustainable delivery of drugs and increase the drug bioavailabilty to the CNS. NogoA antagonist NG-101 will be used as an active pharmaceutical ingredient (API). Proof of concept studies and initial clinical data have proven the enormous potential of blocking NogoA for spinal cord remyelation and axonal integrity. However, monoclonal antibodies (mAb) like NG-101, do not sufficiently cross the BBB. The sustainable and controlled release of NG-101 to the CNS will be achieved via the transport of embedded polymer particles to the olfactory epithelium, the subsequent release of API and permeation through the olfactory region, the only part of the nasal epithelium which is in direct contact with the brain. The direct transport route from the nasal cavity to the brain, bypassing the BBB, offers an exciting mode of central nervous system (CNS) drug delivery not only for demyelinating disorders but also for other CNS indications, e.g., stroke, neurodegenerative diseases or tumours. The proposed new innovative N2B drug delivery platform is a practical, safe, and minimally invasive technology. It will be exploited for NG-101 and has the potential to be implemented with other APIs with a low CNS bioavailability.

Bio2Brain aims to create a trans-European network of industrially oriented specialists fully trained and experienced, a significant driving force in innovating novel technologies to deliver biopharmaceuticals safely and via the nasal route of administration to the central nervous system (CNS). Diseases of the CNS and the spinal cord affect around 165 million Europeans with disorders such as Multiple Sclerosis, Alzheimer’s disease and Parkinson’s disease. CNS disorders are often connected with high morbidity, significant side effects, suffering of the patients and their families, as well as an enormous burden on the welfare systems. Therefore, in terms of social sustainability, Bio2Brain contributes to increased benefit for both, the society as whole and particularly for those individuals at a disadvantage through these disorders. A highly critical challenge of CNS diseases is the low central availability drugs in general and in particular of biopharmaceuticals like monoclonal antibodies (mAbs). Hence, approved medicinal products with a low CNS bioavailability are currently delivered via intrathecal, intracerebroventricular or intraparenchymal injections. In this way, they are delivered directly to the CNS. Unfortunately, such delivery systems are invasive, require a surgery with high risks, have a low patient compliance and are poorly controllable. Therefore, there is a critical need for a more safe and effective new approach, that means a paradigm shift, for drug delivery technologies in the treatment of CNS diseases. The Bio2Brain network will create a research environment for the interdisciplinary and intersectorial training of 13 ESRs supported by 11 academic teams (beneficiaries and partner universities), 6 key industrial stakeholders and an academic non-profit organization. As an important benefit, the close and frequent exposure of the ESRs to the private sector and to key technologies will significantly enhance their employability.