目的 制备盐酸环丙沙星壳聚糖纳米粒原位凝胶，并评价其抑菌及创面愈合效果。方法 采用复乳法制备盐酸环丙沙星壳聚糖纳米粒，采用2因素2水平全因子析因实验设计考察了壳聚糖相对分子质量（X₁）和壳聚糖质量浓度（X₂）对壳聚糖纳米粒的药物包封率（Y₁）、粒径分布（Y₂）、多分散系数（Y₃）和Zeta电位（Y₄）的影响；并以泊洛沙姆407作为凝胶基质制备盐酸环丙沙星壳聚糖纳米粒原位凝胶。通过抑菌圈实验比较盐酸环丙沙星乳膏和盐酸环丙沙星壳聚糖纳米粒原位凝胶对金黄色葡萄球菌和铜绿假单胞菌的抑菌活性；使用无菌活检穿刺针在大鼠背部造成直径为5 mm的皮肤全切除的圆形人工创面，并使用金黄色葡萄球菌和铜绿假单胞菌的培养基感染24 h，建立大鼠创面模型，将模型大鼠随机分为模型组、盐酸环丙沙星乳膏组和盐酸环丙沙星壳聚糖纳米粒原位凝胶组，模型组大鼠创面未接受任何处理，给药组大鼠每2天给药1次，每次给药量均约为1 mg，观察并记录每组大鼠创面脱痂时间和愈合时间。结果 选择低相对分子质量壳聚糖、壳聚糖质量浓度为2.0 mg·mL^-1制备盐酸环丙沙星壳聚糖纳米粒，其中盐酸环丙沙星质量浓度为50.0 mg·mL^-1，其包封率为（85.3±0.9）%，平均粒径为（354.7±15.7）nm，PDI为0.357±0.014，Zeta电位为（22.2±0.5）mV，呈球状分布；盐酸环丙沙星壳聚糖纳米粒原位凝胶和盐酸环丙沙星乳膏对金黄色葡萄球菌的抑菌圈直径分别为（38.4±0.2）、（29.2±0.3）mm，对铜绿假单胞菌抗菌圈直径分别为（41.3±0.6）、（32.1±0.1）mm；大鼠创面给予盐酸环丙沙星壳聚糖纳米粒原位凝胶后，其脱痂时间和愈合时间均较模型组和盐酸环丙沙星乳膏组显著缩短（P<0.05）。结论 成功制备盐酸环丙沙星壳聚糖纳米粒原位凝胶，其可以抑制创面细菌繁殖、加速伤口愈合。

Objective To prepare ciprofloxacin hydrochloride chitosan nanoparticles in situ gels (CHCNSG), and to evaluate its antibacterial and wound healing effect. Methods The ciprofloxacin hydrochloride chitosan nanoparticles were prepared by double emulsion method. The effect of chitosan molecular weight (X₁) and chitosan concentration (X₂) on the encapsulation efficiency (Y₁), particle size distribution (Y₂), polydispersity coefficient (Y₃) and Zeta potential (Y₄) of chitosan nanoparticles was investigated by 22 full factorial factorial experimental design. The CHCNSG were prepared with poloxamer 407 as the gel matrix. The antibacterial activities of ciprofloxacin hydrochloride cream and CHCNSG against Staphylococcus aureus and Pseudomonas aeruginosa were compared by bacteriostatic circle assay. A sterile biopsy needle was used to create a circular artificial wound with a diameter of 5 mm for total skin resection on the back of rats. The rat wound model was established after 24 h infection with the medium of S. aureus and P. aeruginosa. The model rats were randomly divided into model group, the ciprofloxacin hydrochloride cream group and CHCNSG group. The wounds of the rats in the model group were not treated with any treatment, and the wounds of the rats in the administration group were given the drug once every two days, with the dose of about 1 mg each time. The eschar removal time and healing time of the wounds of rats in each group were observed and recorded. Results The ciprofloxacin hydrochloride chitosan nanoparticles prepared with low molecular weight chitosan at a concentration of 2.0 mg·mL^-1, and the mass concentration of ciprofloxacin hydrochloride was 50.0 mg·mL^-1, and it had an encapsulation efficiency of (85.3±0.9)%, average particle size of (354.7±15.7) nm, PDI of (0.357±0.014) and Zeta potential of (22.2±0.5) mV. The ciprofloxacin hydrochloride chitosan nanoparticles were observed to have a spherical distribution under the transmission electron microscope. The diameters of antibacterial zones of CHCNSG and ciprofloxacin hydrochloride cream against S. aureus were (38.4±0.2) and (29.2±0.3) mm, respectively, and the diameters of antibacterial zones against P. aeruginosa were (41.3±0.6) and (32.1±0.1) mm, respectively. The scab removal time and healing time of wound rats treated with CHCNSG were significantly shorter than those of model group and ciprofloxacin hydrochloride cream group (P<0.05). Conclusion CHCNSG was successfully prepared, which can inhibit the propagation of bacteria in wounds and accelerate wound healing.

R943