Localized Drug Delivery System For The Treatment Of Cancer

Abstract

Localized drug delivery can provide better treatment for residual cancer tumors. Our research proposes a “package within a package” drug delivery system which results in an effective controlled release of the drug to the targeted site and also reduces its toxic effects to other parts of the body. The first part of the system is a non-ionic surfactant vesicle or niosome and the second a biodegradable and temperature sensitive crosslinked hydrogel. The vesicle is prepared by hydration of amphiphilic films with a PBS buffer solution and a fluorescent marker, 5,6-carboxyfluorescein. We chose to encapsulate this particular marker to imitate and test the release rate of the chemotherapy drug from the vesicle interior. After hydration, the vesicles were extruded to constrict their size distribution. Unentrapped dye was removed using ultracentrifugation and gel exclusion chromatography. The dye encapsulated vesicles were placed in a semi-permeable cellulose membrane and immersed in a solution of either PBS or Milli-Q water. The environment in the PBS solution would closely mimic the vesicle's behavior in the hydrogel and the water environment would closely follow the behavior near a residual cancer site, where the pH tends to be lower compared to blood. Diffusion of the dye through the membrane was determined at different time intervals by using fluorescence spectroscopy and its release rate was determined. The maker encapsulated niosomes will then be embedded into the hydrogel network which will begin to degrade with time exposing the niosomes to a different pH that will cause them to rupture. The thermal sensitive hydrogel is a polymer, chosen to be Chitosan. Chitosan is a biomaterial obtained abundantly in nature. This system will then have antibodies to provide specificity. Using this methodology, we hope to provide a better treatment technique for cancer patients.