Chemistry, Health & Medicine

Smart drug delivery via microcapsules could lead to safe cancer tumor treatment

Today, cancer is typically treated through highly invasive, painful and low efficiency treatments. Doctors resect the tumors, do radiation therapy, and then chemotherapy. This process is actually more stressful and painful to the patient than the cancer itself, but it does save lives sometimes. Scientists all over the world are hard at work developing alternative treatments, and a recent breakthrough by researchers at  Penn State  makes a significant contribution in this direction.

Perfect microspheres were produced using 4 percent by weight of the polymer. (c) Mohammad Reza Abidian

Mohammad Reza Abidian, assistant professor of bioengineering, chemical engineering and materials science and engineering, along with colleagues designed tiny spherical microcapsules that are biodegredable and can be used for targeted treatment of cancer tumors.

Chemotherapy by intravenously inserting toxic drugs meant to kill the tumors. The big problem with chemo is that the procedure isn’t targeted, and the drugs need to be introduced through out the whole bloodstream affecting the whole body. Moreover, for the drugs to reach the tumor and work their magic, they need to  cross the blood brain barrier. This isn’t easily breached so high doses of the toxic drugs needs to be injected, resulting in even more collateral damage to the body.

“We are trying to develop a new method of drug delivery,” said Abidian. “Not intravenous delivery, but localized directly into the tumor site.”

Other methods have been tested to deliver  BCNU (bis-chloroethylnitrosourea) – the alkylating agent used in chemotherapy – directly into the brain. One such method involves  leaving wafers infused with the anti-tumor agent  in the brain after surgery, but when the drugs in these wafers run out you need to repeat surgery to get them out. Every surgery comes with hazards, besides adding a further complicated step in the treatment process (makes it more expensive), so this method hasn’t been to popular.

This is a scanning electron micrograph of BCNU-loaded microspheres (black and white background) with 3D rendered images of brain cancers cells (yellow) and released BCNU (purple). (c) Mohammad Reza Abidian

Penn State researchers propose an alternate method of treatment. The BCNU agent has a half life in the body of 15 minutes, so insertion in the brain naturally implies that the compound needs to be protect somehow. Their solution is to wrap the BCNU inside biodegradable polymers of spherical shape, which can then be injected directly on the tumor site through the scalp. Now, the idea isn’t new – it’s been employed by other researchers before, however previous solutions involved microcapsules that weren’t uniform in size.

Hitting cancer right in the bull’s eye

It’s paramount for the drug to disperse in an uniform fashion, and this distribution is directly related to the shape. The more uniform the shape of the microcapsule, the better the drug distribution. The microcapsules designed by Abidian and fellows are almost perfectly spherical -  a height versus width ratio of 1.05. This means they can be used to  precisely control the time of drug release by altering polymer composition.

The microcapsules were made using a technique called electrojetting in which a solution (in our case, the  FDA-approved biodegradable polymer poly(lactic-co-glycolic) acid; the BCNU drug; and a solvent)  are rapidly ejected through a tiny nozzle with the system under a voltage as high as 20 kilovolts but with only microamperage.  Under the dissipated heat, the solvent in the solution quickly evaporates leaving behind the microcapsules that can take on the form of anything from a perfect sphere to a fiber, depending on the polymer concentration in the solution. A 3 to 4 percent  by weight solution of the polymer rendered the best results, however the researchers note that other shapes might interest manufactures for other applications.

Microfibers were produced using 10 percent by weight solutions of the polymer. (c) Mohammad Reza Abidian

“Electrojetting is a low cost, versatile approach,” said Abidian. “We can produce drug-loaded micro/nano-spheres and fibers with same size, high drug-loading capacity and high drug-encapsulation efficiency.”

Promising smart drug delivery method

The drug delivery has yet to be tested in the lab, however the researchers made a mathematical simulation of the BCNU drug diffusion from the microcapsules. This helps in designing how much drug to include in each microcapsule and how long the microcapsules will deliver the required dosage. Trials on lab animals might begin shortly. Also important of note is that other drugs, besides BCNU, could be used for treating various afflictions.

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  • Guillermo Vera

    What is the difference between this and chemoembolization through the use of microspheres that has been around for 10 years now?