STEALTH PLA-PEG NANOPARTICLES AS PROTEIN CARRIERS FOR NASAL ADMINISTRATION

Purpose. The aim of the study was to encapsulate a model protein antig en, tetanus toroid (TT), within hydrophobic (PLA) and surface hydrophi lic (PLA-PEG) nanoparticles and to evaluate the potential of these col loidal carriers for the transport of proteins through the nasal mucosa . Methods. TT-loaded nanoparticles, prepared by a modified water-in-oi l-in-water solvent evaporation technique, were characterized in their size, zeta potential and hydrophobicity. Nanoparticles were also assay ed in vitro for their ability to deliver active antigen for extended p eriods of time. Finally, I-125-TT-loaded nanoparticles were administer ed intranasally to rats and the amount of radioactivity recovered in t he blood compartment, lymph nodes and other relevant tissues was monit ored for up to 48 h. Results. PLA and PLA-PEG nanoparticles had a simi lar particle size (137-156 nm) and negative surface charge, but differ ed in their surface hydrophobicity: PLA were more hydrophobic than PLA -PEG nanoparticles. PLA-PEG nanoparticles, especially those containing gelatine as an stabilizer, provided extended delivery of the active p rotein. The transport of the radiolabeled protein through the rat nasa l mucosa was highly affected by the surface properties of the nanopart icles: PLA-PEG nanoparticles led to a much greater penetration of TT i nto the blood circulation and the lymph nodes than PLA nanoparticles. Furthermore, after administration of I-125-TT-loaded PLA-PEG nanoparti cles, it was found that a high amount of radioactivity persisted in th e blood compartment for at least 48 h. Conclusions. A novel nanopartic ulate system has been developed with excellent characteristics for the transport of proteins through the nasal mucosa.