COMBINATION THERAPY FOR CANCER TREATMENT USING MULTICOMPONENT DRUG AMPHIPHILE SYSTEMS

Cancer is a devastating and pervasive disease demanding new treatment strategies.While systemic delivery methods suffer from low drug solubility, low concentration at target site, and systemic side effects, these difficulties can be circumvented with the use of local delivery systems. In this study, drug amphiphiles of camptothecin (TT-6) and paclitaxel (RCP-5) were used to develop four different combination systems aiming to release therapeutics in controlled and unique ways.By mixing the TT-6 and RCP-5 at a monomeric level, filaments equally comprising both monomers were formed. During release studies, it was found that this system released both prodrugs at the same linear rate. By mixing TT-6 and RCP-5 fibers, however, a hydrogel was formed that released both TT-6 and RCP-5 monomers at two unique linear rates, which was controlled by the critical micelle concentration(CMC) of each fiber. In the third design, TT-6 hydrogel was physically embedded within the RCP-5 hydrogel, resulting in a delayed release of TT-6, though the re-lease of both monomers was still governed by the CMC. In the final system, free drug was combined the RCP-5 hydrogel, which resulted in a rapid release of free drug concurrently with the linear release of RCP-5. These different systems show promise for the rational design of multicomponent local drug delivery systems for localized chemotherapy