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 5 0 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 Objective To prepare nasal mucosa melatonin gelatin microspheres to improve its bioavailability. Methods The melatonin gelatin microspheres were prepared by emulsion cross-linking technique. The radionuclide 99mTc was labeled with γ-ray scintigraphy to investigate the residence time of the microspheres in the nasal mucosa. The drug absorption in vivo was determined by HPLC. Results The particle size of melatonin gelatin microspheres was 30-70 μm, the average particle size was 502 μm, and the content of melatonin was 13 48%. Compared with nasal drops, gelatin microspheres significantly prolonged residence time in the nasal mucosa. The absolute bioavailability of melatonin gelatin microspheres was 87 47%. Conclusion Nasal mucosa administration of gelatin microspheres can avoid the first pass of the liver, prolong the residence time of the drug in the nasal mucosa and improve the absorption of drugs, which has a good prospect of application