Development of dry protein powder for intranasal delivery to brain via olfactory and respiratory regions

Abstract

The purpose of this study was to develop and characterize dry protein powder for nose-to-brain drug delivery. Bovine serum albumin (BSA) was selected as a model protein. A novel technique utilizing low energy process equipped with comminutions was used to prepare dry protein powder. Six selected formulations were pulverized, and then powder morphology, physicochemical interactions, mucoadhesive properties, in vitro drug release, and permeation through porcine olfactory and respiratory mucosae were carried out. The results indicated that obtained powders from jet milling had roundish edge and median particle size of about 6.4-9.4 micron with narrow size distribution. Furthermore, there was no new or significant peak shift observing from thermograms, X-ray diffractrograms, and Fourier transform infrared spectra. Powder formulations tended to have better mucoadhesive properties than a control. Protein integrity determination revealed that low energy process made a scarcely detrimental effect on protein secondary structure. On the other hand, the comminution had a potential impact. Only S-6 formulation containing polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer and polyethylene glycol (60% w/w) could maintain protein secondary structure. Additionally, in vitro permeation study showed that native BSA labeled fluorescence (FITC-BSA) solution had slightly higher permeation than powder formulation with no statistical significance. In respiratory mucosa, recovery amount of FITC-BSA from powder formulation was lower than that from solution formulation. It could be explained that powder formulation enhanced permeation through the mucosa more than solution, proven by histological study under fluorescence microscope. According to the results, dry protein powder formulation prepared by low energy process and appropriate comminution seem to be a promising and potential intranasal delivery system for brain targeting.