Using Nanoparticle Shape as a Parameter in Drug Delivery

Abstract

Nanoparticle drug delivery systems encounter many biological barriers, such as mucus gels and the extracellular matrix, that they must bypass in order to gain access to target cells. With this, there is a need to design drug delivery systems to overcome these obstacles to increase their efficacy and retention. One parameter that has recently been looked into is nanoparticle shape, as due to their anisotropic shape, they will experience a drag force along the longer axis, giving them preferential motion along that direction, and higher diffusion and penetration through biological gels. This phenomenon has been demonstrated in gastrointestinal mucus, but the optimal dimensions and aspect ratio of nanoparticles to enhance this effect has yet to be established. To systematically approach this, fluorescent carboxyl-coated polystyrene rod-shaped nanoparticles were synthesized by stretching 100 nm, 200 nm, and 500 nm spherical nanoparticles. Transmission electron microscopy showed that the procedure yielded a combination of rods and spheres then separated by shape via centrifugation. Fluorescent microscopy and multiple particle tracking analysis was then used to characterize rod-shaped and spherical nanoparticle diffusion. In water, rod-shaped particles for all sizes exhibited lower diffusion rate, but when dispersed in MaxGel, an extracellular matrix-based hydrogel, rod shaped nanoparticles exhibit higher diffusion rate. These results would suggest that nanorods can better penetrate biological hydrogels, and thus would have a higher retention and efficacy than comparably-sized nanospheres. The results of this work establish the importance of shape in the design of nanomedicine.