Self-exploding capsules enable timed drug delivery

Researchers at Ghent University and the Université catholique de Louvain have developed "self-exploding" microcapsules which release drugs at a desired time after ingested. Now one can inject drugs and vaccines weeks or months before the body needs its activity. These findings appear in the January 9, 2006 issue of the American Chemical Society's journal Biomacromolecules.

Bruno De Geest, lead author of the paper, said the recent development will replace booster injections, which are a second or later dose of vaccination given to increase the immune response of the original drug. For example, a simultaneous injection of three groups of these microcapsules, each group exploding at a well-defined time after injection, may result in three drug pulses from a single injection. A pulsed delivery implies transmission in small bursts or pulses.

"One may be able to design a drug formulation which delivers the drug in a number of pulses after a single injection," Geest said. "At the moment there are no technologies available which could deliver several drug pulses after a single injection, therefore our technology would pioneer."

These newly developed microcapsules are 5-15 micrometers in diameter, which is one-tenth the thickness of human hair. They feature a biodegradable gel core surrounded by a fat membrane. Cross-linked polysaccharide chains having multiple glucose molecules (dextran) form the gel core. The biodegradable microgels encapsulate drugs/ macromolecules such as proteins or vaccines. The fat membrane surrounds the microgel by interaction of positive and negative charges of the membrane and the gel (electrostatic force.) As the gel biodegrades, a pressure builds up in the membrane. Eventually the microcapsule ruptures, releasing the medication.

After the drug enters into the body, water in the body breaks the bonds between the cross-links in the gel, causing it to decompose. When the gel degrades, the membrane elasticity decreases and the swelling pressure increases. The pressure causes the microcapsule to rupture and release the encapsulated drug.

To tailor the time of explosion of the lipid-coated microgels, the composition (cross-link density) of the microgel can be altered.

Unlike some other microcapsules which release their drug cargo only when exposed to ultrasonic waves (sound waves vibrating with very high frequency) or another external trigger, the new system relies on internal body mechanisms to do the same job.

"The uniqueness of our concept is the fact that our self-exploding microgels do not need an external trigger to explode," Geest said. "Other systems are almost always dealing with systems requiring stimulus in pH, electric field, laser, etc. in order to induce drug release."

- By Pooja Ghatalia.

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