Hydrophilic polymer drug from a derivative of salicylic acid: synthesis, controlled release studies and biological behavior.
Hydrophilic polymeric drugs bearing "Triflusal" (4-trifluoromethylsalicylic acid), a drug widely used as antithrombogenic agent (Disgren), have been prepared by free radical copolymerization of methacryloyloxyethyl [2-(acetyloxy)-4-(trifluoromethyl)] benzoate (HTRF) and N,N'-dimethylacrylamide (DMA). The reactivity ratios of both monomers have been determined by 1H NMR spectra by applying non-linear least square treatments to the copolymerization equation (terminal model), and the kinetic parameters obtained indicated that the microstructure of copolymer chains is homogeneous, with a random distribution of the active HTRF units along the copolymer chains. That means that for the copolymer system THDMA22 used in this work, HTRF units are mainly isolated in relatively long DMA sequences. Therefore, in this structure the intramolecular interactions between adjacent HTRF units are negligible. Release of Triflusal from THDMA22 has been studied in vitro using buffered solutions at pH = 2, 7.4 and 10 and 37 degrees C. The system showed an interesting pseudo-zero order release profile at pH = 7.4 during several months. It has been also evaluated the pharmacological activity and the behavior of the system in contact with biological media. In this sense, we have carried out some in vitro studies about the antiaggregant properties and biocompatibility of THDMA22. Results demonstrate that this copolymer inhibits platelet aggregation in its macromolecular form and presents a good biocompatibility with Human Osteoblastic Cells (HOS).
Instituto de Ciencia y Tecnología de Polímeros (CSIC), c/Juan de la Cierva 3, 28006 Madrid, Spain. gema@ictp.csic.es
Gema
G
Rodríguez
Alberto
A
Gallardo
Mar
M
Fernández
Mercedes
M
Rebuelta
Julia
J
Buján
Juan María
JM
Bellón
Natalio G
NG
Honduvilla
Cristina
C
Escudero
Julio
J
San Román
D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D010006:Osteoblasts / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*; D010974:Platelet Aggregation / Q000187:drug effects; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020156:Salicylic Acid / Q000737:chemistry*
D004364:Pharmaceutical Preparations; D011108:Polymers; D020156:Salicylic Acid