Synthesis and release of 5-fluorouracil from poly(N-vinylpyrrolidinone) bearing 5-fluorouracil derivatives.
1-beta-allyloxycarbonyloxymethyl-5-fluorouracil (4) and 1,3-bis(beta-allyloxycarbonyloxymethyl)-5-fluorouracil (5) were synthesised by reacting 5-fluorouracil with formaldehyde followed by treating the product with isopropenyl chloroformate. The monomers 4 and 5 were copolymerized separately with N-vinylpyrrolidinone to form linear copolymers and cross-linked polymer networks, respectively. The monomer reactivity ratios in the copolymerization of 4 with NVP were evaluated by both linear and non-linear methods and the effect of monomer feed composition on copolymer molecular weight was examined. The degradation of the polymer networks in phosphate buffer (pH 7.4) was investigated. The hydrolytic scission of the carbonate groups resulted in release of 5-fluorouracil and a decrease in cross-linking density. The time-dependent fractional release of the 5-FU could be fitted by a power relationship with exponents between 0.10 and 0.25.
Liu
Zuifang
Z
Department of Chemistry (The Polymer Centre), University of Sheffield, Dainton Building, Brook Hill, S3 7HF, Sheffield, UK.
Rimmer
Stephen
S
D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis / Q000493:pharmacokinetics; D004355:Drug Stability; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D011108:Polymers / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011760:Pyrrolidinones / Q000737:chemistry / Q000493:pharmacokinetics*
D000964:Antimetabolites, Antineoplastic; D011108:Polymers; D011760:Pyrrolidinones; C042670:N-vinyl-2-pyrrolidinone; D005472:Fluorouracil