The Controlled Release of 5-Fluorouracil from Annealed Monolithic Systems
For many years we have been studying the preparation, polymerization and copolymerization of monomers, such as [EMCF] or [EMCM], which contain the anti-cancer drugs 5-fluorouracil [5FU] and 6-methylthiopurine [6MTP], respectively. These polymers and copolymers release the drugs in a zero-order kinetic pattern. In our recent research, 5-fluorouracil [5FU] was monolithically distributed in a poly(caprolactone) [PC] matrix and the release profiles, into water, were studied as a function of the internal phase and temperature. Good, linear plots of the total release against the square root of time (Higuchi kinetics) were followed by these monolithic systems up to about 25–30% [5FU] internal phase. Beyond that point, the systems showed a marked curvature in the release profiles. In the present paper, the effect of annealing the [FUPC] systems was also investigated. These annealed samples showed the same basic release profiles as the unannealed samples, except the release times were much longer (i.e., the slopes of the Higuchi plots were smaller). Monolithic systems that would have released the [5FU] in less than a week, sometimes required more than two months after annealing. Our studies have shown that much greater amounts of [5FU] can be incorporated into the copolymeric systems than into monolithic systems. E.g., an [EMCF] homopolymer contains 45+% [5FU] and still exhibits zero-order kinetics. The potential utility of such systems with higher concentrations and extended time release ranges in long term chemotherapy is obvious.
KeywordsRelease Profile Methyl Acrylate Butyl Acrylate Internal Phase Copolymer System
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