(100g) Distribution Profile of Spherical Drug Carriers and Red Blood Cells in Micro-Vessels

Introduction: Drug delivery systems show great potential to reduce adverse effects and maximize effectiveness of a drug.  A novel approach currently being researched involves polymeric particles that will assist in the distribution of the drug to the target site. It is believed that the non-symmetric branching of arterioles and smaller blood vessels require blood constituents to be skimmed off the periphery of flow to be delivered to specific tissues. This suggests that particles with the greater ability to interact with the red blood cells and be forced to the near-wall fluid layer have a larger potential to branch off into the smaller vessels. In my work, I study the ability of spherical drug carriers to distribute through blood flow to determine the effect of particle size on the distribution. Additionally, the distribution of the red blood cells is also determined at physiologic blood flow conditions.

Method: We investigated the distribution profile of polystyrene spherical particles (500 nm and 2 µm in diameter) and red blood cells in flow chambers (50 µm height) by confocal microscopy. Particles were captured by speed camera in vertical stacks every 2.5 µm height throughout chambers during blood flow. A small percentage of red blood cells were stained with Wheat Germ Agglutinin Alexa Fluor 488 for visualization and were tracked in a similar manner. The human washed blood was fixed at 30% hematocrit in phosphate buffer and flowed under 500s^-1 and 1000s^-1 shear rates. The pictures were then analyzed to determine the amount of particles or cells found in the vertical slice.

Results: It was discovered that when both sized particles are run in phosphate buffer, a normal distribution occurs resulting in the majority of the particles found in the middle of flow.  Red blood cells are also distributed normally within the chamber. However, the spread of the red cells is much less than the particles with only 10% of the cells outside the center half of flow.  After introducing RBCs into the system the 2 µm polystyrene spheres spread to the wall of the chamber, resulting in a larger percent of particles found outside 12.5 µm from the center of flow. This affect was not seen with 500 nm spheres. The results suggest that 2 µm particles interact with RBCs, pushing particles into plasma cell free layer (CFL). Conversely, 500 nm particles were trapped in RBCs bulk flow. This trend was confirmed using confocal microscopy of both particles and labeled red blood cells at the edge of flow.

Conclusion: This work demonstrated the distribution profile of spherical drug carriers in a micron-sized blood flow system can be significantly influenced by particle shape. This inequality for particles of varying size to reach the periphery of flow may hinder the ability of particles to distribute within the body as blood vessels do not bifurcate symmetrically. Future work will evaluate the effect of particle size to distribute in asymmetrical branched channels.