Direct nanodrug delivery for tumor targeting subject to shear-augmented diffusion in blood flow

• Published in: Medical & biological engineering & computing 2018-11, Vol.56 (11), p.1949-1958
• Main Authors: Xu, Zelin, Kleinstreuer, Clement
• Format: Article
• Language: English
• Subjects: Arteries; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Blood flow; Cancer; Computer Applications; Computer Simulation; Diffusion; Diffusion effects; Drug delivery systems; Drug Delivery Systems - methods; Erythrocytes; Feeding; Hepatic artery; Human Physiology; Humans; Hydrodynamics; Imaging; Injection; Liver cancer; Mathematical models; Microspheres; Nanoparticles; Nanoparticles - administration & dosage; Neoplasms - drug therapy; Original Article; Particle Size; Pharmaceutical Preparations - administration & dosage; Radiology; Regional Blood Flow - physiology; Shear; Side effects; Size effects; Transport; Tumors; Veins & arteries
• ISSN: 0140-0118; 1741-0444
• DOI: 10.1007/s11517-018-1818-z

The advent of multifunctional nanoparticle has enabled numerous innovative strategies in diagnostics, imaging, and cancer therapy. Despite the intense research efforts in developing new nanoparticles and surface bonding ligands, one major obstacle in achieving highly effective treatment, including minimizing detrimental side effects, is the inability to deliver drug-carrying nanoparticles from the injection point directly to the tumor site. The present study seeks to employ a direct nanodrug delivery methodology to feed multifunctional nanoparticles directly to tumor vasculatures, sparing healthy tissue. An important aspect to examine is how the interactions between such nanoparticles and relatively large red blood cells would affect the transport and delivery efficiency of nanodrugs. So, a novel computer simulation model has been developed to study nanoparticle transport in a representative human hepatic artery system, subject to shear-induced diffusion of nanoparticles due to hydrodynamic interactions with red blood cells. The particle-size effect was also evaluated by comparing the dynamics of nanoparticles with microspheres. Results from computer simulations under physiologically realistic conditions indicate that shear-induced diffusion has a significant effect on nanoparticle transport, even in large arteries. Nevertheless, as documented, direct nanodrug delivery to tumor-feeding hepatic artery branches is feasible. Graphical abstract Direct nanodrug delivery from injection point to tumor-feeding artery branch