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Drug Delivery May Become Safer

Originally Published MDDI May 2005 R&D DIGEST  

Originally Published MDDI May 2005

R&D DIGEST

Brendan Gill

Larger than viruses, these
natural cell vaults could offer options for targeted drug delivery.

Researchers at UCLA's David Geffen School of Medicine have found a way to store large amounts of biomaterials in cells' natural “vaults.” The vaults, so called for their cathedral-like high arches, are large ribonucleo-protein particles naturally occurring as nanocapsules inside cells. The development could lead to a safer, more targeted way of delivering therapeutic drugs to cells.

“The early applications will probably be drug or DNA delivery or maybe protein stabilization,” says Leonard Rome, PhD, one of the research team's authors.

Other possible uses include sensor applications. “We can envision the particle bringing back some cellular information,” adds Rome. “Some of the things that could be measured are pH and glucose concentration.”

The scientists, headed by Rome and Valerie A. Kickhoefer, associate research biochemist, hope to lower two hurdles in drug-delivery applications. One is specificity, or delivering the nanocapsule to the proper location. The other is controlled release, or getting the cell to deliver the right amount of material.

The nanocapsules can store thousands of drug molecules.

One advantage the cells' vaults have over more- traditional drug- delivery materials is that they occur naturally. Engineered materials, such as viruses, liposomes, peptides, and polymers, have run into problems because they provoke the body's immune system.

“The problem with viruses is that cells will mount an immune response,” says Kickhoefer. “We hope that this cell vault will not mount such a response.”

The nanocapsules also have more storage room than viruses, measuring approximately 50 million cubic angstroms. This enables scientists to store 200–300 large proteins in the cell, or thousands of molecules of a drug. Although the research is encouraging, Rome says, it is not conclusive whether engineered materials, or vaults, are better at drug delivery than other methods. Still, the research has opened the door to many possibilities.

“It's interesting that these [vault nanocapsules] could be engineered and maintain functionality,” says Jeffrey Zink, professor of chemistry at UCLA. “Because we could show that these molecules are sequestered inside the vault, now we can imagine all the other chemicals that could be sequestered inside, and how that could lead to a new type of drug-delivery system.”

Potential applications for the discovery include:

• Therapeutic-drug delivery, such as homing cancer drugs directly to a tumor cell without harming healthy tissue.
• Enzyme delivery to replace missing or defective enzymes, such as those that cause Tay-Sachs disease.
• DNA delivery to correct genetic mutations.
• Timed release of drugs, enzymes, and DNA.
• Extracting and then imprisoning cellular toxins in the vaults.
• Stabilizing proteins in vaults to increase their life spans.

Copyright ©2005 Medical Device & Diagnostic Industry

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