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周元植, 卢雯, 杨倩倩, 等. 一种载药壳聚糖抗菌止血海绵的制备及其性能研究[J]. 四川大学学报(医学版), 2024, 55(1): 190-197. DOI: 10.12182/20240160403
引用本文: 周元植, 卢雯, 杨倩倩, 等. 一种载药壳聚糖抗菌止血海绵的制备及其性能研究[J]. 四川大学学报(医学版), 2024, 55(1): 190-197. DOI: 10.12182/20240160403
ZHOU Yuanzhi, LU Wen, YANG Qianqian, et al. Preparation and Performance Study of a Novel Antibacterial Hemostatic Chitosan Sponge[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(1): 190-197. DOI: 10.12182/20240160403
Citation: ZHOU Yuanzhi, LU Wen, YANG Qianqian, et al. Preparation and Performance Study of a Novel Antibacterial Hemostatic Chitosan Sponge[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(1): 190-197. DOI: 10.12182/20240160403

一种载药壳聚糖抗菌止血海绵的制备及其性能研究

Preparation and Performance Study of a Novel Antibacterial Hemostatic Chitosan Sponge

  • 摘要:
    目的 本研究拟制备一种新型壳聚糖抗菌止血海绵(novel chitosan antibacterial hemostatic sponge, NCAHS),并对其材料学特性和生物学性能进行评价。
    方法 以壳聚糖为海绵基材,添加不同比例三聚磷酸钠(sodium tripolyphosphate, STPP)、甘油、酚磺乙胺,并使用冷冻干燥法制备海绵,以全血凝血指数(BCI)为指标筛选壳聚糖及添加物的最佳浓度获得的止血海绵;在止血海绵中负载盐酸环丙沙星的玉米醇溶蛋白/碳酸钙复合微球(Zein/CaCO3)制备得到NCAHS。采用扫描电镜观察NCAHS的微观形貌、孔隙率,并检测其吸水率、体外对金黄色葡萄球菌(Staphylococcus aureus, S. aureus)和大肠杆菌(Escherichia coli, E. coli)的抗菌率、体外凝血性能、血液相容性。使用兔肝损伤和兔耳动脉损伤出血模型评价止血效果,以市售止血海绵(commercial hemostatic sponge, CHS)作为对照。参照医疗器械生物学评价国家标准检测NCAHS浸提液的细胞毒性,动物皮肤刺激性和体内急性毒性等体内生物相容性。
    结果 以1.5%壳聚糖(质量浓度)、0.01%STPP(质量浓度)、体积分数0%甘油(不添加甘油)、体积分数0.15%酚磺乙胺、Zein和CaCO3质量混合比为5∶1、Zein终质量浓度为2.5 g/L、乙醇终浓度为17.5%(体积分数)制备所得NCAHS细密均匀,具有蜂窝状多孔结构,孔径约200 μm,其BCI数值最低。NCAHS吸水率〔(2362.16±201.15)% vs. (1102.56±91.79)%〕、体外凝血性能(31.338% vs. 1.591%)均优于CHS(P<0.01)。在体内兔耳动脉出血模型〔(36.00±13.42) s vs. (80.00±17.32) s 〕和兔肝脏出血模型〔(30.00±0 ) s vs. (70.00±17.32) s 〕中,NCAHS止血时间均短于CHS(P<0.01)。NCAHS对S. aureusE. coli具有明显的抑制能力,且NCAHS体内外生物相容性良好。
    结论 NCAHS是一种具有优异抗菌性能和止血效果且生物相容性良好的复合海绵,可用于临床推广。

     

    Abstract:
    Objective To create a novel chitosan antibacterial hemostatic sponge (NCAHS) and to evaluate its material and biological properties.
    Methods Chitosan, a polysaccharide, was used as the sponge substrate and different proportions of sodium tripolyphosphate (STPP), glycerol, and phenol sulfonyl ethylamine were added to prepare the sponges through the freeze-drying method. The whole-blood coagulation index (BCI) was used as the screening criterion to determine the optimal concentrations of chitosan and the other additives and the hemostatic sponges were prepared accordingly. Zein/calcium carbonate (Zein/CaCO3) composite microspheres loaded with ciprofloxacin hydrochloride were prepared and added to the hemostatic sponges to obtain NCAHS. Scanning electron microscope was used to observe the microscopic morphology and porosity of the NCAHS. The water absorption rate, in vitro antibacterial susceptibility rate against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), in vitro coagulation performance, and hemocompatibility of NCAHS were examined. The coagulation performance of NCAHS was evaluated by using rabbit liver injury and rabbit auricular artery hemorrhageear models and commercial hemostatic sponge (CHS) was used as a control. The in vivo biocompatibility, including such aspects as cytotoxicity, skin irritation in animals, and acute in vivo toxicity, of the NCAHS extracts was examined by using as a reference the national standards for biological evaluation of medical devices.
    Results The NCAHS prepared with 1.5% chitosan (W/V), 0.01% STPP (W/V), 0% glycerol (V/V), 0.15% phenol-sulfonyl-ethylamine (V/V), Zein and CaCO3 at the mixing ratio of 5∶1 (W/W), Zein at the final mass concentration of 2.5 g/L, and ethanol at the final concentration of 17.5% (V/V) were fine and homogeneous, possessing a honeycomb-like porous structure with a pore size of about 200 μm. The NCAHS thus prepared had the lowest BCI value. The water absorption (2362.16±201.15 % vs. 1102.56±91.79%) and in vitro coagulation performance (31.338% vs. 1.591%) of NCAHS were significantly better than those of CHS (P<0.01). Tests with the in vivo auricular artery hemorrhage model (36.00±13.42 s vs. 80.00±17.32 s) and rabbit liver bleeding model (30.00±0 s vs. 70.00±17.32 s) showed that the hemostasis time of NCAHS was significantly shorter than that of CHS (P<0.01). NCAHS had significant inhibitory ability against S. aureus and E. coli. In addition, NCAHS showed good in vitro and in vivo biocompatibility.
    Conclusion NCAHS is a composite sponge that shows excellent antimicrobial properties, hemostatic effect, and biocompatibility. Therefore, its extensive application in clinical settings is warranted.

     

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