Conforti A, Bertani S, Lussignoli S, Grigolini L, Terzi M, Lora S, Caliceti P, Marsilio F, Veronese F M
Istituto di Farmacologia, Universit-a di Verona, Italy.
J Pharm Pharmacol. 1996 May;48(5):468-73. doi: 10.1111/j.2042-7158.1996.tb05956.x.
A biocompatible and biodegradable polyphosphazene bearing phenylalanine ethyl ester, imidazole and chlorine (10.7:1:2.5 molar ratio) as substituents of the phosphorus atoms of the polymer backbone was studied for 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, respectively, with 20 and 13.5% naproxen, showed different drug release kinetics, 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 induced both 1 h and 7 days after implantation. Rats implanted with thick matrices 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. Blood levels of naproxen in arthritic rats after matrix implantation showed the presence of drug up to day 28. These positive results have encouraged us to study a controlled-release system suitable for use in man.
研究了一种生物相容性和可生物降解的聚磷腈，其聚合物主链磷原子的取代基为苯丙氨酸乙酯、咪唑和氯（摩尔比为10.7:1:2.5），用于制备聚合物萘普生缓释系统。直径2.5厘米、厚度分别为0.5毫米（薄）或0.65毫米（厚）的圆盘，分别负载20%和13.5%的萘普生，显示出不同的药物释放动力学，薄基质释放萘普生的速度更快且时间更短。在大鼠体内的研究证明了这两种不同给药系统在抑制急性或慢性炎症疾病方面的药理功效。在大鼠皮下植入薄基质后发现，在植入后1小时和7天均能减轻角叉菜胶性水肿。植入厚基质的大鼠慢性佐剂性关节炎炎症减轻。在皮下给药基质28天后，发现对关节炎性水肿的抑制率约为78%，而在每日口服萘普生后，抑制率为28.7%。基质植入后关节炎大鼠体内萘普生的血药浓度在第28天仍有药物存在。这些积极结果促使我们研究一种适用于人类的控释系统。
