(38d) Engineering Particle Geometry for Target Specific Adhesion Using Simplified Synthetic Microvascular Networks

Designing novel carriers by optimizing important parameters such as size, shape, composition and surface chemistry, and mechanical properties has resulted in remarkable accomplishments in the field of drug delivery and diagnostic imaging. The next step is to elucidate the biological interactions of these carriers. In this study, the effect of particle geometry, which has recently received significant attention, on the transport of particles through the vasculature and adhesion propensity at the target site has been illustrated. Experiments were performed in simplified synthetic microvascular networks that mimic the in vivo environment.

A synthetic system that simulates the vasculature offers great advantage since it allows variation of a single design parameter to study the particle interactions. Hence, a simplified synthetic microvascular network in the form of a bifurcating channel was synthesized by soft lithographic technique for this study. Particles of different shapes (spheres, rods, elliptical disks and oblate ellipsoids) and sizes (1μm, 3μm and 6μm) were fabricated by the film stretching technique. The surface of the channels and the particles were modified using complementary biomolecules to determine the effect of particle shape on receptor mediated adhesion.

The attachment propensity of spheres, elliptical disks, rods and oblate ellipsoids of different sizes was compared in a bifurcating microchannel. It was observed that elongated particles (rods and elliptical disks) exhibit higher adhesion propensity than particles of other shapes and the difference is more pronounced at larger sizes. Increasing the extent of stretching of 3μm elliptical disks from 4 to 6.5 increased the attachment two fold in both the inlet (straight) section of the channel and at the junction. Moreover, particle adhesion at the junction was found to be 3-6 fold higher than the straight sections. Larger particles, due to higher settling velocities tend to attach more (~2 fold) at the inlet compared to smaller particles. Static experiments were also performed where no significant difference in the attachment of particles of different geometry was observed, thus illustrating the importance of studying particles in flow. Further experiments with more complex networks and with cells grown in the microchannels will help understand the interactions better.

Particle geometry plays an important role in transport properties and targeting efficiency of particles. Such information will be useful in optimizing the design of carriers for specific biomedical applications.