Issue Date: May 13, 2013
Drug Delivery With A Bang
Polymer and nanoparticle conjugates have been widely studied for their potential to deliver drugs selectively to specific tissues and organs, but many such conjugates are structurally diverse, and the amount of drug they deliver can be hard to control—characteristics that are not conducive to drug approval.
A new class of conjugates called chain-shattering polymers, which have highly controlled structures and release predictable drug amounts, could help resolve such problems (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201300497). The polymers, developed by Jianjun Cheng and coworkers at the University of Illinois, Urbana-Champaign, could be useful for treating skin lesions, tumors, and other conditions at localized sites and tissues.
Conjugates have often been structurally variable because drugs attach to different numbers of polymer or nanoparticle sites. Chain-shattering polymers, which are made of alternating units of drug and “suicidal” chemical residues, have more highly controlled structure and composition because the drug is an integral part of the polymer backbone. In the presence of an ultraviolet or peroxide trigger, a protecting agent is removed from each suicidal group, causing polymer chain shattering and near-complete drug release, making the amount of drug supplied more predictable.
“This is the only polymeric nanomedicine I know that has nearly perfect control over composition, structure, and release profile,” Cheng says. “We are interested in commercializing the technology.”
Drug delivery specialist Kathryn Uhrich at Rutgers University and coworkers previously designed PolyAspirin, in which the aspirin is also incorporated directly into the polymer backbone. Cheng’s group combined that concept with chain shattering to release drug molecules on demand. They demonstrated 80% release of camptothecin, an anticancer agent, in about 10 minutes.
Uhrich says “the chemistry is clever—relatively simple and broadly applicable to various functionalities” but notes that in vivo delivery, formulation stability, possible side effects from polymer degradation, and other factors still need to be demonstrated or evaluated.
Chun Li, a drug delivery expert at the University of Texas M. D. Anderson Cancer Center, says chain shattering “can deliver high drug payloads, the release is sharp, and it can be done in a highly controlled fashion.” Capabilities for intravenous administration and targeting of specific tissues and organs are important areas for future evaluation, he notes.
UV radiation doesn’t penetrate tissue easily but has potential for treating skin lesions, whereas peroxide can be generated internally and therefore has potential for internal treatments. Cheng’s group is also trying to develop triggers based on near-infrared radiation, which penetrates tissue more deeply than UV does.
If the polymers can be harnessed effectively in vivo, they could have “a lot of potential benefits therapeutically,” says Todd Emrick, a specialist in polymer therapeutics at the University of Massachusetts, Amherst.
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