title: Development of Novel Polymeric Prodrugs Synthesized by Mechanochemical Solid-State Copolymerization of Hydroxyethylcellulose and Vinyl Monomers.
abstract: Novel polymeric prodrugs were synthesized by mechanochemical solid-state copolymerization of hydroxyethylcellulose and the methacryloyloxy derivative of 5-fluorouracil (5-FU). Copolymerization was about 94% complete after 4 h, and the polymeric prodrug was quantitatively obtained after 14 h of reaction. The number average molecular weight (Mn) and polydispersity (H) of the polymeric prodrug were 39000 g/mol and 6.20, respectively. Mechanical fracturing of the polymer in a stainless steel twin-shell blender improved these properties (Mn=16000 g/mol and H=1.94). 5-FU was sustainably released from the polymeric prodrugs, and the rate was not affected by the molecular weight or molecular weight distribution of the prodrug under the experimental conditions used. These results suggest that novel polymeric prodrugs composed of a polysaccharide and a synthetic polymer can be fabricated by mechanochemical solid-state copolymerization under anaerobic conditions.
authors.affiliation: Laboratory of Pharmaceutical Physical Chemistry, Gifu Pharmaceutical University.
authors.forename: Naoki
authors.initials: N
authors.lastname: Doi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasai
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kuzuya
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Kondo
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D006868:Hydrolysis; D055595:Mechanical Phenomena; D015394:Molecular Structure; D008970:Molecular Weight; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D011108:Polymers; D011355:Prodrugs; D014753:Vinyl Compounds; D002482:Cellulose; C002283:hydroxyethylcellulose