【摘要】 目的:以脱乙酰壳聚糖为载体,制备了粒径分别为120,350和1000 nm的胰岛素生物粘附性微球并考察各类微球对四氧嘧啶糖尿病大鼠的降血糖作用.方法:采用离子趋向凝胶化方法制备了粒度不同的各类微球.光子相关光谱法及光学显微镜法测定了各类微球粒径及粒度分布.考察了处方各因素对微球粒径大小和载药量的影响及各类微球的体外释药特性.以葡萄糖氧化酶法测定血糖浓度来评价各类微球口服给药后对糖尿病大鼠的降血糖作用.结果:制备微球粒径均在所需范围,载药量分别为15.3％±1.7％(120 nm),32.4％±2.4％(350nm),53.3％±2.7％(1000 nm).粒径对微球的体外释放特性有一定的影响,0.5h后各类微球释放25％±4％(120 nm),18.3％±2.4％(350 nm),8.6％±1.3％(1000 nm).口服给药10 h后,各类微球均表现出明显的降血糖作用(P<0.05).15 h,粒径为350 nm微球所引起的降血糖作用明显高于120 nm;350 nm的微球与其它微球比,35 h后,仍具有显著的降血糖作用(P<0.01).与皮下注射相对照,口服各类微球的相对生物利用度分别是10.2％± 0.5％(120 nm),14.9％± 1.3％(350 nm),7.3％±0.8％(1000 nm).t检验结果表明,口服350 nm微球的生物利用度明显高于其它粒度的微球(P<0.05).结论:生物粘附性壳聚糖微球能够提高胰岛素的相对生物利用更多还原

【Abstract】 AIM: To formulate and characterize insulin-loaded adhesive microspheres (MP) and evaluate drug effects of MP with various sizes, 120, 350, and 1000 nm in diameter, in the alloxan-induced diabetic rats. METHODS: Insulin-loaded MP were formulated by an ionotropic gelation procedure. Particle size distributions were determined by photon correlation spectroscopy and optical microscopy. The factors that influenced the particle sizes and loading capacity were investigated, and the release properties were assessed in vitro. The hypoglycemic effect was inves-tigated by monitoring the plasma glucose level of the alloxan-induced diabetic rats after oral administration. RESULTS: All the MPs with three sizes formulated were in the desired size range, and the loading capacity was 15.3 %?.7 % (120 nm), 32.4 %?.4 % (350 nm), and 53.3 %?.7 % (1000 nm) respectively. The particle size also had an influence on the release property of the MPs. Half an hour later, 25 %? % (120 nm), 18.3 %?.4 % (350 nm), and 8.6 %?.3 % (1000 nm) of insulin were released. MP with different sizes had various degree of hypoglycemic effects after 10 h (P<0.05 vs control insulin solution). The plasma glucose level of 350 nm size particles remarkably decreased 15 h later (P<0.05 vs 120 nm) or 35 h later (P<0.01 vs others). The relative pharmacological availability was 10.2 %?.5 % (120 nm), 14.9 %?.3 % (350 nm), and 7.3 %?.8 % (1000 nm) respectively. Particles of 350 nm showed a comparatively higher availability (P<0.05). CONCLUSION: Adhesive CS-MP were helpful in increasing the relative pharmacological bioavailability of insulin, and a distinct advantage of proper particle size helped to increase the drug effects.更多还原