HOUSTON, May 26, 2005 - Chemical engineers from Rice University have developed a fundamentally new approach - the most environmentally sensitive yet devised - for making tiny hollow spheres called microcapsules. Microcapsule research is one of the most active fields in applied nanotechnology, with dozens of companies either developing or using the tiny containers - usually smaller than living cells - to deliver everything from drugs and imaging agents to perfumes and flavor enhancers.
In research appearing on the cover of this month's issue (Vol. 17, Issue. 9) of the journal Advanced Materials, Michael Wong and his research group describe an approach for making microcapsules that involves mixing a solution of polymer and salt with tiny particles of silica that contain just a few hundred atoms apiece.
Microcapsules are typically made by depositing layers of a coating onto a template or core, which has to be removed to form the hollow center of the structure. The core is usually burned out with high heat processes or dissolved with harsh chemicals. Both processes can damage both the microcapsules and their cargo.
"Our process takes place almost instantaneously, at room temperature, under normal pressure, in water, and at mild pH values," said Wong, assistant professor of chemical and biomolecular engineering, and chemistry. "The spheres naturally become hollow during the self-assembly, which is highly unusual and is an advantage over existing methods."
Wong's approach has advantages over other microcapsule production methods that involve spraying techniques. While these techniques can be scaled up, it is difficult to adjust the materials properties of the resulting microcapsules.
"We've shown that we can tailor the properties of our self-assembled microcapsules - make them smaller, larger, thicker or thinner - simply by changing the ingredients we start with or by adjusting the mixing procedure," Wong said. "The underlying chemistry is so easy to perform that anyone who can pour, mix, and shake can make these microcapsules in less than a minute."
Wong's process involves 'self-assembly,' meaning the hollow spheres form spontaneously when the nanoparticle building blocks are mixed with polymer and salt. Because the process takes place in water, any chemical or drug that's suspended in the water gets trapped inside the hollow sphere when it forms.
Besides encapsulating drugs, flavor compounds and other molecular cargo, Wong's team hopes to develop their microcapsules for drug delivery. They are already exploring ways - like using changes in pH or temperature - to trigger the microcapsules to open and release drugs. In addition, they've made magnetic microcapsules by using iron oxide nanoparticles instead of silica. This could allow doctors to use magnets to precisely position drugs prior to their release.
"We can also use fluorescent nanoparticles called quantum dots to make glowing hollow spheres, which could be useful for combined drug delivery and imaging," Wong said.
Another potential application includes the delivery of medical imaging agents. For example, most contrast agents that doctors use to improve diagnoses from magnetic resonance imaging are highly toxic. If a small quantity can be sealed away in a microcapsule, safe from contact with any living cells, it could alleviate illness and side effects that patients experience today.
The microcapsules could also be used to encapsulate enzymes, complex biomolecules that that govern many cellular processes. Because enzymes are fragile and expensive, engineers would like to protect them during chemical reactions so they can be used many times over.
Wong's group has shown they can do that to by storing enzymes inside the microcapsules. Their data show that enzymes didn't leak through the walls of the microcapsules, but smaller molecules did, meaning the enzymes could still carry out their prime function and act as a catalyst for chemical reactions. Wong believes the technology could be used to make micro-bioreactors that could be used in large-scale chemical or drug production.
"In comparison with the other methods of making microcapsules, the scale-up for our process is simple and inexpensive," said Wong. "We believe this gives us a very competitive advantage over competing processes, and a number of companies have expressed an interest in the process."
Wong's research was funded by Halliburton Energy Services. Oak Ridge Associated Universities, Kraft Foods and Rice University
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