Researchers from Penn State University are working to develop a new method of drug delivery based on consistently uniform, easily manufactured microcapsules, which would be particularly applicable to treating patients with brain caner. The majority of chemotherapy is done intravenously, but, because the drugs are toxic and are not targeted, they have a lot of side effects. Another problem with intravenous drugs is that they go everywhere in the bloodstream and do not easily cross the blood brain barrier so little gets to the target tumors. For some brain cancer, the chemotherapy is delivered locally to the site. Current treatment already includes leaving wafers infused with the anti-tumor agent BCNU in the brain after surgery, but when the drugs in these wafers run out, repeating invasive placement is not generally recommended. BCNU has a half life in the body of 15 minutes. The medication needs protection because of the short half life. Encapsulation inside biodegradable polymers can solve that problem. Encapsulation of BCNU in microspheres has been tried before, but the resulting product did not have uniform size and drug distribution or high drug-encapsulation efficiency. However, with uniform spheres, manufacturers can design the microcapsules to precisely control the time of drug release by altering polymer composition. The tiny spheres are also injectable through the skull, obviating the need for more surgery. The researchers are using an electrojetting technique to encapsulate BCNU in poly(lactic-co-glycolic) acid, an FDA-approved biodegradable polymer. In electrojetting, a solution containing the polymer, 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. The solvent in the liquid quickly evaporates leaving behind anything from a perfect sphere to a fiber. The researchers tested solutions of polymer from 1 percent by weight to 10 percent by weight and found that at 1 to 2 percent they obtained flattened microspheres, at 3 to 4 percent they had microspheres, at 4 to 6 percent they had microspheres and microfibers, at 7 to 8 percent they had beaded microfibers and above 8 percent they obtained only fibers. Depending on the desired applications, most of the shapes are useful. While fibers are not good for drug delivery, they are good for tissue engineering applications. The researchers also investigated the sphericality of the spheres. They have a height versus width ratio of 1.05 and they have size uniformity. A perfect sphere would have a ratio of 1. The researchers also looked into how BCNU releases from the microcapsules. The researchers established a drug diffusion coefficient for the encapsulation system. This helps in designing how much drug to include in each microcapsule and how long the microcapsules will deliver the required dosage. The researchers note that BCNU is not the only drug that can be encapsulated in polymer beads for drug delivery. Other drugs can be used but would have their own diffusion coefficients and half lives.
www.eurekalert.org/pub_releases/2013-09/ps-mpu082913.php
