New biodegradable networks of poly(N-vinylpyrrolidinone) designed for controlled nonburst degradation in the vitreous body

Polymers of N-vinylpyrrolidinone (NVP) are known to have excellent biocompa tibility when implanted in the vitreous body or used as a vitreous substitu te. Al though poly(NVP) is capable of absorbing relatively large amounts of water, it is not prone to hydrolysis. Yet intraocular degradation of sever al crosslinked poly(NVP) hydrogels has been reported recently, but some amb iguity remains about the exact mechanism of degradation of these materials. To date there is no biomaterial that combines the excellent intraocular bi ocompatibility on the one hand and controlled kinetics of degradation on th e other hand. We attempted to design and prepare such materials through the chemical synthesis of a novel dimethacrylate crosslinker molecule. The ess ential feature of this molecule is that its core contains two carbonate gro ups, which are evidently susceptible to hydrolytic scission. We studied a s eries of 3-dimensional networks of poly(NVP), which were crosslinked by thi s molecule. This approach offers several advantages: the hydrolysis of the carbonate groups in the crosslinks leads to liberation of poly(NVP) and/or oligo(NVP) chains that can probably be cleared from the eye via phagocytosi s; hydrolysis generates two alcohols and CO2 (i.e., there is no catalytic b urst effect); when these materials are implanted in dry form, swelling and degradation will progress from the exterior of the material toward its inte rior. Therefore, these materials can be designed such that surface degradat ion rather than bulk degradation occurs; the hydrolysis rate can be control led via the crosslink density or through synthesis of other crosslink molec ules with either more (>2) or less (1) carbonate groups or alternatively wi th one or more other labile groups. We report on the chemical synthesis of the crosslinker molecule, as well, as the preparation and degradation of a series of poly(NVP)-based hydrogels in vitro and in vivo (rabbit eyes). We found that these materials indeed displayed excellent biocompatibility in t he rabbit eye. Further, the experiments confirmed that degradation occurs w ithout the burst effect. The results are in line with the idea that the rat e of intraocular swelling and degradation depends on the crosslink density, but this is only a preliminary conclusion that must be strengthened by muc h more experimental work. Nonetheless, we foresee several applications of t hese or related materials in ophthalmology, for example, as biodegradable m atrix materials for controlled drug delivery of ganciclovir in the vitreous body. (C) 1999 John Wiley & Sons, Inc.