ANTIINFLAMMATORY ACTIVITY OF POLYPHOSPHAZENE-BASED NAPROXEN SLOW-RELEASE SYSTEMS

A biocompatible and biodegradable polyphosphazene bearing phenylalanin e ethyl ester, imidazole and chlorine (10.7:1:2.5 molar ratio) as subs tituents of the phosphorus atoms of the polymer backbone was studied f or the preparation of polymeric naproxen slow-release systems. Discs 2 .5 cm in diameter and 0.5 mm (thin) or 0.65 mm (thick), loaded, respec tively, with 20 and 13.5% naproxen, showed different drug release kine tics, the thin matrices releasing naproxen at a faster rate and for a shorter time. In-vivo studies in rats demonstrated the pharmacological efficacy of these two different delivery systems in the inhibition of acute or chronic inflammatory diseases. Subcutaneous implantation of the thin matrices in rats was found to reduce carrageenan oedema induc ed both 1 h and 7 days after implantation. Rats implanted with thick m atrices showed a reduction in chronic inflammation caused by adjuvant arthritis. Approximately 78% inhibition of arthritic oedema was found 28 days after subcutaneous administration of the matrices whereas 28.7 % inhibition was found after daily oral administration of naproxen. Bl ood levels of naproxen in arthritic rats after matrix implantation sho wed the presence of drug up to day 28. These positive results have enc ouraged us to study a controlled-release system suitable for use in ma n.