(Nanowerk Spotlight) In diabetes treatment, drug delivery systems are often based on self-assembled micelles that disintegrate when they get in touch with glucose, thereby releasing the insulin molecules that have been trapped inside. This is a passive mechanism by which the drug release is based solely on diffusion.
In contrast, an active mechanism pumps out the drugs in response to a specific stimulus, e.g. an insulin pump responding to blood sugar fluctuations.
Researchers at Penn State, led by Professor Ayusman Sen have now demonstrated an active glucose-responsive self-powered fluidic pump based on transesterification – the conversion of a carboxylic acid ester into a different carboxylic acid ester – reaction of acyclic diol boronate with glucose.
"The scientific principle of our project is to use well-known glucose/boronate chemistry to design a self-powered micropump device," Dr. Hua Zhang, a member of Sen's group and the paper's first author, tells Nanowerk. "Instead of synthesizing some new molecules with glucose/boronate reaction, we fabricated a miniature pump that utilizes the energy of this chemical reaction and pumps drugs when glucose levels are high."
Schematic demonstration of the experimental setup. (a) Transesterification inside the micropump when exposed to glucose. (b) Normal configuration of the micropump: outward fluid flow on the top layer (near the horizontal boundary opposed to the pump) and inward flow on the bottom layer (near the glass slide). (c) When the micropump is flipped upside down, flow direction reverses: outward fluid flow on the top layer (near the glass slide) and inward flow on the bottom layer (near the horizontal boundary opposed to the pump). (Reprinted with permission by American Chemical Society)
Apart from demonstrating a drug delivery mechanism which actively pumps out small molecules, the team also provided a solution to one of the challenging aspects of current self-powered nanomotor/micropumps research – the issue of the power source.
Most micropump devices are simply too small to carry their own fuels. A practical solution is to design these devices so that they can consume fuels from their environment.
"In the past, many of these devices could only use toxic chemical fuels," notes Zhang. "In our paper, we prove that biofriendly fuel – glucose – can be used in these systems. Our micropump is capable of converting chemical energy into mechanical motion directly."
To fabricate their glucose-responsive micropump, the researchers used a hydrogel material. "This makes the micropump highly hydrophilic so that the glucose molecules in aqueous solution have sufficient access to the hydrophobic acyclic diol boronate moieties in the pump matrix," explains Zhang.
This kind of device might become useful for advanced drug delivery system, better wound care formulation, and power-free lab-on-chip applications.
Sen, whose group has been investigating self-powered nanomotors and -pumps for several years (see for instance our previous Nanowerk Spotlight: "Titanium dioxide powers light-driven micro- and nanomotors"), hopes to compile a library of devices that can perform active transportation and pumping tasks of various complexities.
"We’d like to drive our research in two directions," he says. "One is to investigate the detailed mechanisms of such systems and come up with better and more accurate modeling. The other direction is to bring in other chemistry to build new devices with different capability. In addition, the Defense Threat Reduction Agency (DTRA) is interested in developing these pumps to release antidotes in response to the presence of nerve agents in the environment."