目的 基于質量源于設計（QbD）理念制備鹽酸洛美沙星殼聚糖納米粒（LF-CNs），并評價其體外抗菌活性。方法 采用離子凝膠化法制備LF-CNs，根據失效模式效應分析（FMEA）工具初步評估影響LF-CNs制劑性質的潛在處方和工藝變量，并通過2水平部分析因實驗設計篩選出影響LF-CNs制劑性質的關鍵變量，最終以殼聚糖濃度、三聚磷酸鈉（STPP）濃度和攪拌速度3個獨立變量作為考察因素，以LF-CNs的粒徑分布和包封率作為評價指標，應用Box-Behnken實驗設計優(yōu)化并得到LF-CNs的處方和制備工藝參數。通過Zetasizer Nano ZS 90動態(tài)激光粒度儀測定LF-CNs的粒徑分布、聚合物分散性指數（PDI）和ζ電位，透射電子顯微鏡下觀察LF-CNs的微觀形態(tài)；采用體外透析法考察LF-CNs和LF原料藥體外藥物釋放特性；通過抑菌實驗比較LF原料藥與LF-CNs的體外抑菌活性。結果 經實驗優(yōu)化得到LF-CNs的最優(yōu)處方和工藝參數：殼聚糖質量濃度為10 mg/mL，STPP質量濃度為6 mg/mL，攪拌速度為750 r/min；在透射電鏡下可觀察到LF-CNs呈圓球狀，無聚集，粒徑大小為（479.6±18.7）nm，PDI為（0.194±0.012），ζ電位為（34.4±1.9）mV，LF-CNs的體外釋放機制符合Korsmeyer-Peppas方程擬合，藥物的釋放為擴散和溶蝕雙重機制；LF-CNs對金黃色葡萄球菌的體外抑菌效果優(yōu)于LF原料藥。結論 將鹽酸洛美沙星制備成殼聚糖納米粒，處方設計科學合理，制備工藝簡單易行，體外抑菌活性顯著，有望成為鹽酸洛美沙星眼用給藥的一種有效途徑。

Objective To prepare lomefloxacin hydrochloride chitosan nanoparticles (LF-CNs) based on the concept of quality by design (QbD), and evaluate its in vitro antibacterial activity. Methods LF-CNs were prepared by ionic gelation method. Using the failure mode effect analysis (FMEA) tool to identify the potential formulation and process variables that affect the properties of LF-CNs. The key variables that affect the properties of LF-CNs were screened by 2-level factorial experiment design. Finally, the three independent variables of chitosan concentration, STPP concentration and stirring speed were used as the investigating factors, and the particle size distribution and encapsulation efficiency of LF-CNs were used as evaluation indicators. The formulation and process parameters of LF-CNs were optimized and obtained using Box-Behnken experimental design. The particle size distribution, ζ potential and in vitro drug release characteristics of LF-CNs were investigated. The antibacterial activities of LF raw materials and LF-CNs in vitro were compared through the inhibition zone experiment. Results The optimal formulation and process parameters of LF-CNs were optimized by experiment: The chitosan concentration was 10 mg/mL, the STPP concentration was 6 mg/mL, and the stirring speed was 750 r/min. Under the transmission electron microscope, it could be observed that LF-CNs were spherical, without aggregation, the particle size was (479.6±18.7) nm, the PDI was (0.194±0.012), the ζ potential was (34.4±1.9) mV, and the in vitro release rate of LF-CNs can be fitted by Korsmeyer-Peppas equation. The in vitro antibacterial effect of LF-CNs on Staphylococcus aureus was higher than that of LF raw materials. Conclusion In this study, lomefloxacin hydrochloride was prepared into chitosan nanoparticles. The formulation design was scientific and reasonable, the preparation process was simple and easy, and the antibacterial activity in vitro was significant. It is expected to become an effective way of ophthalmic administration of lomefloxacin hydrochloride.

R962.2