Controlled spherical crystallography for targeted drug delivery
4 May 2020
Results from a research collaboration between researchers at Drexel’s College of Engineering and the Chemistry Department at the University of Tennessee, Knoxville demonstrate how to control the formation of structures like polymer crystal spheres by mixing chemicals in a solution - rather than physically manipulating their growth. The discovery is part of a broader design effort focused on the encapsulation of medicine for targeted drug treatments.
"Most crystals grow in a regular pattern, if you think about snowflakes, there is a translational symmetry that guides the unit cell repeating throughout the crystalline flake. What we've discovered is a way to chemically manipulate the macromolecular structure so that this translational symmetry is broken when the molecule crystallises," Li said. "This means we can control the overall shape of the crystal as it forms - which is a very exciting development, both for its scientific significance and the implications it could have for mass production of targeted therapies."
The technique Li uses to compel what would normally be a flake-like crystal to draw itself up into a sphere builds on his previous work with polymers that look like brushes and polymer crystals formed from emulsion droplets. Incorporating these pliable ‘bottle-brush’ polymers as the structural system of the crystal, allows Li to shape its growth by adjusting the "bristles" of the brush.
"A bottle-brush polymer has lining bristles surrounding a spine, what we discovered is that we can make that spine bend upon crystallisation by packing bristles on to one side of it," Li said. "This sets the pattern that is repeated as the crystal grows - so instead of growing flat it curves three-dimensionally to form a sphere."
This means the amount of bristle polymers in the solution will determine how much the bottle-brush spine bends and thus the shape and size of the crystal ball.
Li's team also reports on how to pause the formation of the crystal, leaving holes in the sphere that could be useful for inserting a medicinal payload during the manufacturing process. Once filled, it can be closed with polymers tailored to help direct it to its target in the body.
"We have been working toward this achievement for some time," Li said. "This spherical crystallography manifests itself in robust structures that we see in nature from eggshells to virus capsids, so we believe it is the ideal form to survive the rigours of delivering medication in the body. Being able to control the properties of the crystal as it forms is an important step toward realising this application."
The original paper, Breaking translational symmetry via polymer chain overcrowding in molecular bottlebrush crystallization, was co-authored by Christopher Li, PhD, and Bin Zhao, PhD, and was recently reported in the scientific journal Nature Communications.
