November 6th, 2012
A Hitchhiker’s Guide to Drug Delivery
By Emily Frangenberg | Comments (1)
A novel drug delivery technique has nanoparticles thumbing for a ride aboard red blood cells.
Major roadblocks are frequently encountered in nanoparticulate drug delivery systems; short circulation times often send the nanoparticles to the liver and spleen in a matter of a few minutes, and due to this, the particles rarely end up at their target destination. Surface modification, encapsulation, and attachment of specific ligands to the nanoparticle have been studied as ways to enhance nanoparticulate performance, though none show as much promise as the research being conducted at the University of California, Santa Barbara.
A team led by Dr. Samir Mitragotri
has developed a way to harness the flexibility and mobility of red blood cells to overcome the short circulation times and poor targeting associated with nanoparticles.
Drug delivery for treatment of respiratory ailments
Mitragotri began the study by attaching nanoparticles to the surfaces of red blood cells. Particles ranging from 200–500 nm adhered to red blood cell surfaces through electrostatic and hydrophobic interactions. Several in vitro
trials were performed to determine the ideal shape and curvature of the nanoparticles for adhesion.
An in vivo
study proved the potential viability of this technique for drug delivery. Twice as many nanoparticles were deposited in the lungs as in the liver after 10 hours when attached to red blood cells; for nanoparticles alone, this ratio was below 0.1. It was discovered that the method of deposition was purely mechanical: the lung’s small capillaries sheared the nanoparticles off the red blood cell, without compromising the red blood cell itself. This study has the potential to greatly enhance targeted drug delivery to treat respiratory ailments.
Hitchhiking on monocytes and macrophages
Another study evaluated some of the body’s even smaller cell types – monocytes and macrophages – for diseased tissue penetration. Unlike red blood cells, these small cells are able to pass into tumors and other diseased tissue easily, so they hold great potential for cancer treatment. However, they have a tendency to internalize and digest whatever small particles they come into contact with. So attaching a nanoparticle, and keeping that nanoparticle from being essentially eaten, was a major challenge. By modifying the angles and volume of the nanoparticle, Mitragotri determined that at a certain point, the monocyte/macrophage can’t stretch around the nanoparticle and therefore cannot internalize it.
Research showed that the best shape to prevent internalization was a long, flat disk – nicknamed a backpack. Both macrophages and monocytes accepted more than one backpack, and still behaved normally after detachment. Although research is still being conducted, it is hoped that when these cells pass into tumors and diseased tissue, the backpacks will be deposited directly into the tumors.