A Better Way to Deliver Cancer Drugs
A paper-thin, biodegradable implant is proving an effective way to attack cancer cells without punishing the body with chemotherapy. The implant is a clear, flexible film that can be designed in any shape or size. A key ingredient in the film is chitosan, which is derived from a natural material extracted from algae and the exoskeletons of shellfish.
Researchers at the University of Toronto have developed a way to dissolve a high concentration of various cancer-fighting drugs within the film, which is then applied directly to a site where a tumor has been removed. The drugs, which are loaded into polylactide nanoparticles, are control-released over several weeks as the implant breaks down in the body. “The formulation appears to be quite flexible,” says Micheline Piquette-Miller, an assistant professor of pharmaceutical sciences at the university and codeveloper of the drug-delivery system. “We can incorporate very diverse types of chemicals into it, and that’s what a lot of other systems have had trouble with.”
Piquette-Miller and her team are currently focusing their research on ovarian cancer, which has a high relapse rate and typically requires several rounds of chemotherapy following tumor removal.
Cancer drugs administered orally or intravenously often don’t reach the right organ or region of the body in strong enough doses. By applying a high concentration of cancer-fighting agents directly to a tumor site, the drugs are more likely to kill the target cells.
“We’re also working on an injectable formulation,” says Piquette-Miller, explaining that an implant could be placed within an area of the body without the need for surgery–ideal for treating prostate, breast, and other forms of cancer. “It’s a liquid gel at room temperature, and it forms an implant once it is injected into the body and reaches 37 degrees Celsius,” she says.
For the past three years, the team has been testing the system on different strains of mice to determine the efficacy of certain drug concentrations. Two weeks ago the researchers received funding to carry out a series of toxicity studies on mice before beginning human testing. Christine Allen, codeveloper and University of Toronto chemical engineer, says the film has been designed to be flexible enough that it won’t puncture internal organs. It’s also completely biocompatible. “One of the problems with past systems like this is they’re seen as foreign by the body, and tissue grows around it,” Allen explains. In this situation, called fibrous encapsulation, the surrounding tissue can often prevent proper drug release or keep the drug from reaching the tumor. “We haven’t had this problem,” she says.
Robert Langer, a chemical engineer at MIT, says that tissue growth can affect how implants deliver drugs, although most systems can handle small amounts of encapsulation. “If [the University of Toronto system] doesn’t have any fibrous encapsulation, that would be an advance,” he says.
Various polymer systems have been developed for the localized delivery of anticancer drugs, but the University of Toronto film is the first formulation to physically cross-link chitosan–widely used as a wound dressing and in artificial skin–with naturally occurring phospholipids. “Chitosan based polymer blends are useful for controlled drug delivery because they degrade uniformly into non-toxic molecules that are non-mutagenic, non-cytotoxic and non-inflammatory,” according to patent documents describing Allen and Piquette-Miller’s approach.
Marcel Bally, a senior scientist with the department of advanced therapeutics at the British Columbia Cancer Agency, says the chitosan-based film has the potential to be translated rapidly into clinical use. “It’s novel and very practical,” says Bally. “What I think is really exciting about this technology is the idea that they’re developing a drug-delivery system that’s designed for multiple drugs, and there’s really not a lot of people doing that right now.” He says drug combinations are proving much more effective at battling cancer, so the ability to deliver such anticancer cocktails locally is key. “I think that’s where drug-delivery systems will play a huge role in the future.”
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