Abstract: Objective:To prepare the sustained release system of icariin(ICA)@gelatin nanoparticles(GNPs)-polyactic-co-glycolic acid(PLGA) (ICA@GNPs-PLGA), and to optimize the conditions. Methods: ICA@GNPs-PLGA sustained release system was prepared using two-step desolvation method and S/O/W emulsion solvent-evaporation technique. The effects of different conditions, such as the PLGA:GNPs mass ratio and the total quality of ICA added on the entrapment efficiency (EE) of ICA@GNPs-PLGA composite microspheres were detected to optimize the preparation process. The surface morphology of GNPs and ICA@GNPs-PLGA composite microspheres were observed by SEM. The EE and the release results of ICA@GNPs-PLGA in the sample were determined with HPLC. Results: The prepared composite microspheres and nanocomplex were were white powder. The SEM results showed that the composite microspheres and nanocomplexs were spherical, the surfaces were smoothy, and the particle size distribution range was 4-12 μm and 150-200 nm, respectively, relatively uniform. At a GNPs mass fraction of 6 mg, the critical concentration of PLGA in DCM ranged within 0.5%-1.0%. At a GNPs mass fraction of 12 mg, the critical concentration of PLGA in DCM ranged within 1.0%-2.0%.However, at a critical PLGA mass fraction lower than 0.25%, no fully formed composite microspheres were observed. Within the critical concentration, the average EE of ICA@GNPs-PLGA microspheres was higher than(62.00±1.25)%. In addition, the EE of ICA in the microspheres was negatively correlated with the quality of ICA added. The accumulative release rate was less than in 24 h and it was 65.21% in 40 d. Conclusion: The ICA@GNPs-PLGA microspheres with homogeneous particle size distribution, high EE, low initial burst and without agglomeration can be acquired under the optimized conditions.

Key words: nanocomplex, microparticles, icariin, poly(lactic-co-glycolic acid, sustained release