Potential role of size and hemodynamics in the efficacy of vascular-targeted spherical drug carriers.
Targeting of drug carriers to the vascular wall is of interest for localized delivery of therapeutics in many human diseases. Nanometer-sized spherical particles are widely proposed for use as carriers for vascular targeting, yet very little evidence has been presented as to their ability to interact with the vascular wall. Thus, this work focuses on elucidating the effect of particle size along with hemodynamics, blood rheology, and vessel size on the adhesion efficiency of targeted polymeric spheres to inflamed endothelium in vitro via parallel plate flow chamber assays. We find that the binding efficiency of spheres to the endothelium from blood flow generally increased with increasing particle size, wall shear rate and channel height for particle sizes from 100 nm up to 10 microm. However, nano-sized particles showed minimal adhesion to the endothelium from blood flow in horizontal (gravity or anti-gravity direction) and vertical channels on the order of small to medium-sized venules and arteries when compared to micron-sized spheres. Furthermore, adhesion of nanospheres was not enhanced with pulsatility in flow. Overall, the presented data suggests that spheres 2-5 microm in size are optimal for targeting the wall in medium to large vessels relevant in several cardiovascular diseases.
Charoenphol
Phapanin
P
Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Huang
Ryan B
RB
Eniola-Adefeso
Omolola
O
D001783:Blood Flow Velocity / Q000502:physiology*; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000737:chemistry*; D005240:Feasibility Studies; D006801:Humans; D008422:Materials Testing; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011137:Polystyrenes / Q000737:chemistry*
D004337:Drug Carriers; D011137:Polystyrenes