目的 制備鹽酸環(huán)丙沙星殼聚糖納米粒原位凝膠，并評價其抑菌及創(chuàng)面愈合效果。方法 采用復(fù)乳法制備鹽酸環(huán)丙沙星殼聚糖納米粒，采用2因素2水平全因子析因?qū)嶒炘O(shè)計考察了殼聚糖相對分子質(zhì)量（X₁）和殼聚糖質(zhì)量濃度（X₂）對殼聚糖納米粒的藥物包封率（Y₁）、粒徑分布（Y₂）、多分散系數(shù)（Y₃）和Zeta電位（Y₄）的影響；并以泊洛沙姆407作為凝膠基質(zhì)制備鹽酸環(huán)丙沙星殼聚糖納米粒原位凝膠。通過抑菌圈實驗比較鹽酸環(huán)丙沙星乳膏和鹽酸環(huán)丙沙星殼聚糖納米粒原位凝膠對金黃色葡萄球菌和銅綠假單胞菌的抑菌活性；使用無菌活檢穿刺針在大鼠背部造成直徑為5 mm的皮膚全切除的圓形人工創(chuàng)面，并使用金黃色葡萄球菌和銅綠假單胞菌的培養(yǎng)基感染24 h，建立大鼠創(chuàng)面模型，將模型大鼠隨機分為模型組、鹽酸環(huán)丙沙星乳膏組和鹽酸環(huán)丙沙星殼聚糖納米粒原位凝膠組，模型組大鼠創(chuàng)面未接受任何處理，給藥組大鼠每2天給藥1次，每次給藥量均約為1 mg，觀察并記錄每組大鼠創(chuàng)面脫痂時間和愈合時間。結(jié)果 選擇低相對分子質(zhì)量殼聚糖、殼聚糖質(zhì)量濃度為2.0 mg·mL^-1制備鹽酸環(huán)丙沙星殼聚糖納米粒，其中鹽酸環(huán)丙沙星質(zhì)量濃度為50.0 mg·mL^-1，其包封率為（85.3±0.9）%，平均粒徑為（354.7±15.7）nm，PDI為0.357±0.014，Zeta電位為（22.2±0.5）mV，呈球狀分布；鹽酸環(huán)丙沙星殼聚糖納米粒原位凝膠和鹽酸環(huán)丙沙星乳膏對金黃色葡萄球菌的抑菌圈直徑分別為（38.4±0.2）、（29.2±0.3）mm，對銅綠假單胞菌抗菌圈直徑分別為（41.3±0.6）、（32.1±0.1）mm；大鼠創(chuàng)面給予鹽酸環(huán)丙沙星殼聚糖納米粒原位凝膠后，其脫痂時間和愈合時間均較模型組和鹽酸環(huán)丙沙星乳膏組顯著縮短（P<0.05）。結(jié)論 成功制備鹽酸環(huán)丙沙星殼聚糖納米粒原位凝膠，其可以抑制創(chuàng)面細(xì)菌繁殖、加速傷口愈合。

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