(342b) Hitchhiking of Nanoparticles On Red Blood Cells for Targeted Delivery to Lungs

Nanoparticulate drug delivery systems are one of the most widely investigated approaches for developing novel therapies for a variety of diseases. However, there are two major roadblocks for clinical interventions of these exciting therapeutic approaches: (i) rapid clearance of foreign materials by the immune system, and (ii) limited ability to target delivery of therapeutics to sites of interest. Here, we describe an approach to harness the flexibility, circulation, and vascular mobility of red blood cells (RBCs) to overcome both of these roadblocks (Cellular Hitchhiking). Anchoring nanoparticles onto the surface of red blood cells has been proven to reduce clearance by the immune system and extend the in vivo circulation time when compared to non-anchored counterparts [1]. In this work, we investigate the potential of “Cellular Hitchhiking” for targeted delivery of therapeutic carriers to the respiratory system via surface attachment of nanoparticles to RBCs. This novel delivery system was evaluated in vitro by characterizing (i) attachment efficiency, and (ii) cellular morphological changes following particle attachment to red blood cells. Time-dependent biodistribution of RBC-anchored nanoparticles was determined in vivo, which exhibited several fold higher lung accumulation compared to that of unattached nanoparticles. Parameters defining mechanisms for enhanced lung accumulation, and its therapeutic potential will be discussed. These results highlight the efficacy of cellular hitchhiking in providing targeted delivery of therapeutic agents for treatment of various cardiopulmonary and respiratory ailments.

1. Chambers, E., & Mitragotri, S., Prolonged circulation of large polymeric nanoparticles by non-covalent adsorption on erythrocytes. Journal of controlled release, 2004, 100(1): pg. 111-119.