Assessing Biodistribution and Transport Mechanisms of Polyanhydride Nanoparticles

Polymeric nanoparticles have become important candidates towards the design of biodegradable adjuvants for vaccine and drug delivery. By providing a means for controlled antigen release without interfering with protein antigen activity, these particles potentially allow for reduction of the number of vaccine doses required to induce protective immunity. Aliphatic polyanhydride copolymers are commonly used for drug delivery applications because of their antigen-mimicking properties. The polyanhydride chemistry of interest for this study was based on sebacic acid (SA) and 1,6-bis(p-carboxyphenoxy)hexane (CPH). Even though the use of CPH:SA copolymer has been proven suitable for vaccine delivery, the exact mechanism by which the administered nanoparticles interact with and initiate immune responses are not yet known. The purpose of this work was to further characterize the kinetics of particle distribution in vivo and determine if and how CPH:SA nanoparticles reach draining lymph nodes (dLNs) following administration. Using live imaging, we tracked the biodistribution of 20:80 CPH:SA nanoparticles following both subcutaneous (SQ) and intranasal (i.n.) administrations. Our data indicates that the site of SQ administration affects the level of particle distribution, likely due to tissue tension and perhaps fluid exchange kinetics. Particle persistence was shown by SQ administration at the foot pad, which is desirable for localized vaccine delivery. This is a key component when long-term localization of the antigen is desired. Our studies regarding i.n. administration of these particles indicate that they could serve as vehicles for the delivery of antigens and/or drugs to the lungs, as it has been previously demonstrated by our group. Biodistribution of nanoparticles to the kidneys, resulting from SQ injections at the nape of the neck, may be related to their absorption into the circulation and deposition into the renal system. This finding can be used for the development of future formulations that may be able to provide targeted renal treatment. Nanoparticle drainage or migration to dLNs was not observed using either ex vivo imaging or flow cytometry at all time points analyzed. Repeat studies should be performed to determine the exact biodistribution of nanoparticles into peripheral organs and utilize other polyanhydride chemistries to determine their effect on biodistribution. Future studies should also assess particle migration/drainage into LNs using other methods that do not require tissue homogenates, such as fluorescence and confocal microscopy.