Polymeric drugs based on random copolymers with antimitotic activity.
Polymeric drugs based on random copolymers with antimitotic activity were obtained by free radical copolymerization of oleyl 2-acetamido-2-deoxy-α-d-glucopyranoside methacrylate (OAGMA) and 2-ethyl-(2-pyrrolidone) methacrylate (EPM) at low and high conversion and analyzed in terms of microstructure, physicochemical, and biological properties. Reactivity ratios of monomers were found to be r(OAGMA) = 1.34 and r(EPM) = 0.98, indicating the obtaining of statistical copolymers with random sequence distribution of the comonomeric units in the macromolecular chains. The glass transition temperature of the copolymers presents a negative deviation from the predicted values according to the Fox equation, suggesting a higher flexibility of the alternating diad. Copolymeric systems with OAGMA contents between 10-50 mol % presented thermosensitive behavior in a heating process showing cloud point temperatures (CPT) in the range 45-28 °C with increasing OAGMA content and hysteresis in one heating-and-cooling cycle. In vitro glycolipid release studies revealed the stability of the ester group in culture medium. The polymeric drugs with 30 and 50 mol % OAGMA presented antimitotic activity on a human glioblastoma line, but they were less toxic on normal human fibroblast cultures.
López-Donaire
M L
ML
Institute of Polymer Science and Technology, CSIC, Juan de la Cierva, 3, 28006 Madrid, Spain.
Parra-Cáceres
J
J
Fernández-Gutiérrez
M
M
Vázquez-Lasa
B
B
Román
J San
JS
D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008689:Methacrylates / Q000737:chemistry*; D008938:Mitosis / Q000187:drug effects*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D050256:Antimitotic Agents; D001672:Biocompatible Materials; D006027:Glycosides; D008689:Methacrylates; D011108:Polymers