褪黑激素明胶微球的鼻腔给药

目的　制备经鼻粘膜给药的褪黑激素明胶微球，以提高其生物利用度。方法　用乳化交联技术制备褪黑激素明胶微球，用放射性核素^99mTc标记，用γ射线闪烁显像技术考察微球在鼻粘膜滞留时间，用HPLC法测定药物的体内吸收。结果　褪黑激素明胶微球粒径在30～70 μm，平均粒径为50.2 μm，褪黑激素含量为13.48%。与滴鼻液相比，明胶微球在鼻粘膜滞留时间明显延长。褪黑激素明胶微球的绝对生物利用度为87.47%。结论　鼻粘膜给药明胶微球，能避免肝脏首过作用，延长药物在鼻粘膜滞留时间，提高药物吸收，有很好的应用前景。

STUDIES ON MELATONIN GELATIN MICROSPHERES FOR INTRANASAL ADMINISTRATION

AIM: To increase the bioavailability of melatonin (MT), MT gelatin microspheres (MT-GMS) for intranasal administration were prepared. METHODS: MT-GMS were prepared using emulsifying-cross linking technique. Orthogonal tests were used to optimize the preparation conditions. The residence time of technetium-99m (99mTc) labeled gelatin microspheres (GMS) in the nasal cavity of rabbits as compared to gelatin solution, was investigated using gamma scintigraphy. Furthermore the bioavailability in rabbits was examined for evaluating MT-GMS. RESULTS: The mean diameter of MT-GMS was 50.2 microns, the particle size focused on 30-70 microns. The drug content was 13.48%. The release profile in vitro showed sustained effect. The residence time of GMS in the nasal cavity of rabbits was longer than that of gelatin solution. After intranasal administration in rabbits, the bioavailability of MT-GMS was 87.47% as compared to vein injection, while the bioavailability of MT solution was 69.72%. CONCLUSION: MT-GMS prepared could meet the needs of intranasal administration, and could increase the bioavailability of MT.