Hetrocyclic methacrylate systems as vehicles for the release of active species.

Abstract

The room temperature polymerising heterocyclic polymer system, poly(ethyl methacrylate)/tetrahydrofurfuryl methacrylate (PEM/THFM) has been shown previously to be biocompatible and supported tissue repair, specifically for bone and cartilage, and biologically inert when in contact with the dental pulp. It proved more effective, than other glassy methacrylates in the release of active species. The PEM/THFM system is a rigid material. The aim of this study was to develop and characterise the use of this system as a flexible patch, for application and retention to the buccal mucosa, thus facilitating sustained regulated release. Model species, dextrans, were used to represent macromolecular drugs whereby the effect of molecular weight could be studied. N-methyl pyrrolidone was added to the polymer system as a biocompatible plasticiser to enhance molecular mobility, and hence the transport of species. The effect of the addition of chitosan was also studied, due to its bioadhesiveness and permeation enhancing ability. A range of systems was investigated both in terms of water and species release. The release of the agent was measured by a fluorometer, the leachable components by HPLC and Confocal microscopy demonstrated the transport of water and active species through the system. Immunological and viability studies established whether the leachants or released components of the polymeric systems had an inflammatory or irritant action on `in vitro' stratified epithelium. The addition of N-methyl pyrrolidone, dextran and chitosan substantially increased water uptake, thus affecting the release kinetics. Analysis of the kinetics of water uptake showed Case I, combination of Case I and Case II, and Case II kinetics, depending on the systems studied. Dextran release was largely diffusion controlled, from which diffusion coefficients were calculated; the amount released varied between the systems studied.