title: In vitro release of 5-fluorouracil with cyclic core dendritic polymer.
abstract: This paper describes the first synthesis of a series of dendritic polymers with a core of 1,4,7,10-tetraazacyclododecane. This core was allowed to react with methyl acrylate through a Michael addition and was then amidated with ethylenediamine. Repeating the two steps led to controlled molecular weight increasing and branching on the molecular level and produced four direction poly(amide-amine) dendrimers. We successfully synthesized dendrimers from generation 0. 5 to generation 5.5. Each generation was analyzed by Fourier- transform infrared (FT-IR) spectroscopy, 1H NMR and elemental analysis. Titrimetry was also used to determine the number of -NH2 of each full generation (2.0, 3.0, 4.0, 5.0). SEC (size exclusion chromatography) was performed to test the purity of G-3.0, G-4.0 and G-5.0. Parts of the outer layer -NH2 groups of the dendrimers generation 4 and generation 5 were acylated by acetic anhydride. The solubility in water of the dendrimer was thus greatly enhanced. The acetylated dendrimers were then reacted with 1-bromoacetyl-5-fluorouracil to form dendrimer-5FU conjugates. Hydrolysis of the conjugates in a phosphate buffer solution (pH 7.4) at 37 degreesC will release free 5FU. Different generation of dendrimer-5FU conjugates exert marking influence on the amount of 5FU released. The dendritic polymer seems to be a promising carrier for the controlled release of antitumor drugs.
authors.affiliation: Department of Chemistry, Laboratory of Biomedical Polymer Materials of the State Education Commission of China, Wuhan University, Wuhan 430072, People's Republic of China.
authors.forename: R X
authors.initials: RX
authors.lastname: Zhuo
authors.forename: B
authors.initials: B
authors.lastname: Du
authors.forename: Z R
authors.initials: ZR
authors.lastname: Lu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry; D002614:Chelating Agents; D000080027:Cyclams; D003692:Delayed-Action Preparations; D005029:Ethylenediamines; D005472:Fluorouracil / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry; D006571:Heterocyclic Compounds; D006868:Hydrolysis; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates; D009757:Nylons; D011108:Polymers; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000964:Antimetabolites, Antineoplastic; D002614:Chelating Agents; D000080027:Cyclams; D003692:Delayed-Action Preparations; D005029:Ethylenediamines; D006571:Heterocyclic Compounds; D008689:Methacrylates; D009757:Nylons; D011108:Polymers; C038072:cyclen; D005472:Fluorouracil