Protein aerosol for intranasal nose to brain (N2B) delivery

Background For the treatment of metabolic and neurodegenerative diseases, drug delivery to the central nervous system (CNS) has gained considerable recent interest [1,2]. But many concepts for the delivery of therapeutic agents have failed by the natural blood-brain barrier (BBB). The N2B route for drugs is able to provide an adequate alternative of CNS drug delivery -bypassing the BBB [3,4]. N2B drug transport takes mainly place at the olfactory cleft, an area that is well hidden in the skull base [5]. In a previous study, we determined the characteristics of aerosols for optimal deposition for N2B delivery by a computational approach and validated those data with experimental deposition in a human nose model generated by rapid prototyping [manuscript in preparation]. With the determined criteria, different aerosol generators were evaluated for protein dispersion. Moreover, a surrogate method was developed that imitates the dispersion effect was used for formulation screening to maintain stability and function and to avoid shear stress during dispersion. The most promising protein formulations were tested in an in vitro exposition system for passage through a nasal epithelium in a transwell culture. This test system can be used to develop an N2B platform approach.