Transport Behavior of Commercial Anticancer Drug Protein-Bound Paclitaxel (Paclicad) in a Micron-Sized Channel.

ABSTRACT

Protein-bound paclitaxel has been developed clinically as one of the most successful chemotherapy drugs for the treatment of a wide variety of cancers. However, these medications, due to their nanoscale properties, may often induce capillary blocking while migrating through minute blood vessels. Considering the detrimental impact of this restriction, we investigated the transport of protein-bound paclitaxel, Paclicad, in a 7 µm microchannel mimicking the identical mechanical confinement of the blood capillaries. The drug was reported to migrate through a constricted microchannel without obstruction at a solution flow rate of 20-50 µL/h. The onset of an agglomeration site was observed at higher flow rates of 70-90 µL/h, while complete capillary obstruction was observed at 100 µL/h. The mobility of the particles was also calculated, and the results suggested that the presence of varying cross-sections affects the mobility of the drug particles. The trajectory of the particle migration was observed to be less tortuous at the higher flow rate, but the tortuous nature appeared to increase with the presence of agglomeration sites in the flow field. The experimental results were also compared with the computational model of the drug particle. The drug particle was modeled both as Newtonian and as an FENE-P viscoelastic drop. The drop interface tracking was done by the VOF method using the open source software Basilisk. The particle displacement was better estimated by both the FENE-P and Newtonian model at a flow rate of 30 µL/h, while deviation was observed at a flow rate of 50 µL/h. The FENE-P model was observed to show higher deformation than the Newtonian model at both flow rates. The experimental results provided better insight into the agglomeration tendency of Paclicad, migrating through a constricted microchannel at higher flow rates. The numerical model could be further employed to understand the more complex intravenous transport of drugs.