Biodegradable three-dimensional networks of poly(dimethylamino ethyl methacrylate). Synthesis, characterization and in vitro studies of structural degradation and cytotoxicity

In ophthalmology, there is a need for novel degradable biomaterials for e.g . controlled drug release in the vitreous body. These degradable materials should feature both excellent biocompatibility, and well-defined kinetics o f degradation. In most cases, poly(D,L-lactic acid), or poly(lactic-co-glyc olic acid) are used. These materials, however, suffer from some serious dra wbacks, since the degradation kinetics are difficult to control, especially since the so-called 'burst-degradation' occurs. Here, we describe a set of novel polymeric networks which largely consist of poly(dimethylamino ethyl methacrylate) (poly(DMAEMA)); these materials are crosslinked via a dimeth acrylate molecule that contains two carbonate groups. This system is suscep tible to hydrolytic scission. The degradation products do nor exert a catal ytic effect on the ongoing degradation reaction (i.e. there is no burst eff ect). We describe the synthesis of three of these materials, which differ m erely with regard to the crosslinker content. These materials were characte rized through DMTA, H-1 NMR and FT-IR spectroscopy, and scanning electron m icroscopy. The reaction DMAEMA + 2-hydroxyethyl methacrylate (HEMA) was stu died in detail, using H-1 NMR spectroscopy, and these experiments revealed that the reaction of DMAEMA and HEMA produces a random (Bernouillian-type) copolymer. From this, we contend that the new materials have more or less u niform distribution of the crosslinks throughout their volume. Structural d egradation of the three materials was studied in vitro, at pH 7.4, 9.1 and 12.0. It is found that the materials exhibit smooth hydrolysis, which can b e controlled via the crosslink density and the pH, as was expected a priori . It should be noted that degradation of these materials produces non-hydro lysable, but water-soluble, oligo(DMAEMA) and poly(DMAEMA) molecules. We su bsequently performed in vitro studies on the biocompatibility of these mate rials. The MTT cytotoxicity assay revealed that the materials were cytotoxi c to chondrosarcoma cells. This is most probably due to local increase of t he pH due to the basic character of the pending dimethylamino groups. Cytot oxicity remained virtually unchanged after extended washing with water. Thi s indicates that the cytotoxicity is an intrinsic property of the material and was not caused by remnants of free monomer. Cytotoxicity was also seen in cell cultures (human fibroblasts isolated from donor corneas) which were grown in contact with the materials. It is concluded that the new material s have attractive degradation characteristics, but their cytotoxicity makes them unsuitable for applications in ophthalmology. (C) 2000 Elsevier Scien ce Ltd. All rights reserved.