353 CRYSTALLIZATION of Paclitaxel IN Hydrogel-BASED Delivery Systems

Thursday, November 5, 2009: 4:40 PM
Pancho Villa (Camino Real Hotel)
Javier S. Castro, Ph.D. , Basic Sciences department, Autonomous University of Juarez City, Juarez, Mexico
Selene Sandoval , Basic Sciences department, Autonomus University of Juarez City, Juarez, Mexico
Carlos A. Martinez, Dr. , Basic Sciences department, Autonomus University of Juarez City, Juarez, Mexico
Pierre A. Deymier, Ph.D. , Materials Science and Engineering, University of Arizona, Tucson, AZ
Recently a variety of drug delivery systems have been proposed for the treatment of tumors by localized delivery of anticancer drugs to the affected area. Some of these drug delivery systems have proposed the use of thermosensitive biodegradable hydrogels containing a drug incorporated into its polymeric matrix. The hydrogel-drug system can be injected in liquid state directly into the tumor, once the hydrogel is in contact with the body, it solidifies and then the drug is released as the hydrogel is degraded into the body. Paclitaxel (Taxol™), one of the most successful anticancer drugs, has been commonly used in these drug delivery systems. One of the main challenges in paclitaxel-based delivery systems is its poor solubility. In aqueous solutions paclitaxel spontaneously  forms   spherulitic and needle like crystals when is used at concentrations above its solubility limit. Some researchers have incorporated paclitaxel directly into hydrogels using concentrations above its saturation limit, which may lead to paclitaxel crystallization into the hydrogels. This crystallization is undesirably because paclitaxel crystals do not dissolve easily into the body and they have been directly associated with allergic reactions. These negative effects may decrease dramatically the expected therapeutic results of the paclitaxel delivery system.
Paclitaxel crystallization has been ignored by many authors working with paclitaxel-based delivery systems, probably because paclitaxel crystals are hard to detect using conventional methods.
In this work, we study the crystallization of paclitaxel in aqueous solutions and hydrogels. We demonstrated that the incorporation of paclitaxel directly into hydrogels using concentrations previously reported leads to paclitaxel crystallization. We also propose an easy, but novel method to detect paclitaxel crystals into hydrogels in order to avoid inefficient paclitaxel-based delivery systems.