(227e) Blood-Cell Inspired Drug Delivery Systems for Improved Delivery of Polymeric Carriers

Authors: 
Anselmo, A. C., Massachusetts Institute of Technology
Mitragotri, S., University of California Santa Barbara

Polymeric particle drug delivery systems are widely explored to improve the biological outcome of encapsulated drugs for therapeutic effects. Unfortunately, nearly all synthetic materials, polymeric particles included, suffer from limited abilities in vivo.  Poor vascular circulation, limited targeting and the inability to negotiate many biological barriers have prevented the overwhelming majority of polymeric particle drug delivery systems from entering the clinic. To further complicate this, the above requisites must be performed simultaneously while also limiting toxic effects to the patient. While it is theoretically possible to design such multifunctional carriers, as Mother Nature has provided us with many examples of successful carriers in the form of circulatory cells, an engineered example capable of these same functions has yet to be demonstrated. Here, to improve the delivery abilities of synthetic carriers we report blood-cell inspired drug delivery systems that are inspired by the natural delivery abilities of the main individual cellular components in blood: (i) erythrocytes (red blood cells), (ii) leukocytes (including monocytes) and (iii) thrombocytes (platelets). Two main strategies are employed to take advantage of blood-cell delivery mechanisms to improve the in vivo functions of synthetic carriers. The first strategy, known as “cellular hitchhiking”, involves attaching synthetic materials (polymeric particles) to the surface of circulatory cells to transfer properties from cell to particle and subsequently alter the in vivo fate of the synthetic particles. Specific in vivo examples of cellular hitchhiking to be discussed include: (i) adsorption of nanoparticles to the surface of red blood cells for both prolonged circulation and lung targeting, and (ii) antibody-mediated attachment of flat disc shaped “cellular backpacks”, fabricated via layer-by-layer assembly, to the surface of monocytes for specific targeting to inflamed tissues. The second strategy, the design of synthetic cells, involves incorporating key biophysical and biochemical design parameters of natural platelets into completely synthetic platelet-like nanoparticles. Synthetic platelets, fabricated via layer-by-layer assembly, mimic the shape, flexibility and complex biochemical interactions of real platelets. The design, characterization and in vivo hemostasis (prevention of blood loss in a tail transection model) abilities of synthetic platelets will be discussed. The use of circulatory blood cells, either: (i) directly, as in the case with cellular hitchhiking, or (ii) indirectly, as in the case with platelet inspired synthetic cells, offers a new design paradigm for nanomedicine.