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. The lead matrix was selected and for the final formulation the particle development started. Novel techniques to evaluate adhesion and spreading of the formulation at the olfactory region were set-up further one. The technology transfer of the galenic formulation was demonstrated by using previously prepared batch production documentation at pilot scales. The pilot scale manufacturing protocol of the antibody-loaded particles and the hydrogel as a product for the application to olfactory region for nose-to-brain delivery of antibodies is ready. The first large scale manufacturing was realized at MyBiotech and Contipro facilities for a batch size representative of industrial scales.
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. This URS has served as the basis for the further evaluation of the assigned properties ensuring the consolidation of an aligned development, once it has been transmuted in a functional design specification. The experimental work on the application process was supported by using 3D casts. The moulding design for the applicator was completed. The respective functional design specifications were based on the URS requirements, matching the physical, the chemical and the mechanical properties as well as the functionality of the CCS together with the N2B matrix patch generated by the computational model output to the experimental feasibility.
A battery of tests was established to determine, if the developed biomaterial and the constructed application system meet the needs and functions needed for a successful intranasal delivery of antibodies. The mechanism of action of the nose to brain transport was investigated, which enables us to rationally design the galenic formulation and potential drug candidates for an optimal central bioavailability. In-vivo models were established, which were successfully used to show proof of concept in an MS model. A profound understanding of drug absorption, uptake, pharmacokinetics (PK) and pharmacodynamics (PD) after intranasal delivery via the olfactory region is vital for a successful development of the N2B-patch platform technique for other CNS active drugs with low central availability.
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. A generic market study on available MS treatments and nose-to-brain applicators as well as a Freedom-to-operate analysis linked to related patents were performed. The patent application of the project partner Beiter was awarded.
Besides general communication activities (e.g. logo, website, Flyer, video animation), N2B-patch is still present in Social Media, e.g. YouTube and LinkedIn.
The consortium attended relevant scientific conferences, held presentations or presented posters related to N2B-patch, this involves patient-related events. Due to the Covid-19 pandemic, mostly all events have been virtual since March 2020.
