Engineered dry powders for the nose-to-brain delivery of transforming growth factor-beta

Nose-to-brain delivery is increasing in popularity as an alternative to other invasive delivery routes. However, targeting the drugs and bypassing the central nervous system are challenging. We aim to develop dry powders composed of nanoparticles-in-microparticles for high efficiency of nose-to-brain delivery. The size of microparticles (between 250 and 350 µm), is desired for reaching the olfactory area, located below the nose-to-brain barrier. Moreover, nanoparticles with a diameter between 150 and 200 nm are desired for traveling through the nose-to-brain barrier. The materials of PLGA or lecithin were used in this study for nanoencapsulation. Both types of capsules showed no toxicology on nasal (RPMI 2650) cells and a similar permeability coefficient (P_app) of Flu-Na, which was about 3.69 ± 0.47 × 10^-6 and 3.88 ± 0.43 × 10^-6 cm/s for TGF-β-Lecithin and PLGA, respectively. The main difference was related to the location of deposition; the TGF-β-PLGA showed a higher drug deposition in the nasopharynx (49.89 ± 25.90 %), but the TGF-β-Lecithin formulation mostly placed in the nostril (41.71 ± 13.35 %).