聚多巴胺空心微球负载环丙沙星抗菌剂的制备及抗感染研究

Preparation and Anti-infection Research of Ciprofloxacin Antibacterial Agent Loaded Polydopamine Hollow Microspheres

关键词:  聚多巴胺  微球  环丙沙星  抗菌  抗感染  伤口愈合

Key words:  polydopamine  microspheres  ciprofloxacin  antibacterial  anti-infective  wound healing

摘要:

目的 制备一种近红外光触发药物释放的新型抗菌剂来对抗细菌感染和促进伤口愈合。方法 通过透射电子显微镜、紫外可见吸收光谱和傅里叶变换红外光谱表征所制备的抗菌剂。对不同浓度的抗菌剂采用近红外光照射，研究抗菌剂的光热性能。通过测定不同条件下药物的释放来研究其释放性能。应用涂布平板法、细菌生长曲线法研究抗菌剂的抗菌活性。用不同的方法对小鼠进行抗感染治疗，观察小鼠伤口愈合的过程，研究其对伤口愈合的影响。结果 合成的抗菌剂在近红外光照射下可重复不衰减升温，在较低浓度125 µg·mL^-1时依然达到45 ℃的高温，在升温的同时能促进所负载抗菌药物的释放，释放率达到86%。与聚多巴胺与环丙沙星200 µg·mL^-1物理混合溶液相比，所合成的抗菌剂联合近红外光展现了更为优异的抗菌能力，对大肠杆菌和金黄色葡萄球菌的抑菌率为99.9%。0.312 5 µg·mL^-1和1.25 µg·mL^-1的抗菌剂联合近红外光照射后也可以明显抑制大肠杆菌和金黄色葡萄球菌的生长。通过金黄色葡萄球菌感染的小鼠皮肤缺损模型验证了该合成抗菌剂在实际应用中仍旧有着优异的抗菌效果，并能加速感染型伤口的愈合。结论 合成的抗菌剂体外光热协同抗菌有着优异的抗菌效果，体内在不引起皮肤损伤的保守功率照射下依然有着良好的抗菌效果并能促进伤口的愈合。

Abstract:

OBJECTIVE To prepare a new antibacterial agent triggered by near infrared light to combat bacterial infection and promote wound healing. METHODS The synthesis of antibacterial agengt was supported by the results from transmission electron microscopy, Ultraviolet-visible absorption spectroscopy and Fourier-transform infrared spectroscopy. The antibacterial agent was irradiated under near infrared(NIR) laser with different concentrations to study the photothermal properties. Release of ciprofloxacin from the antibacterial agent was determined under different conditions. Observed antibacterial activity of the agent by spread plate method and bacterial growth curve. The infected wound was made on the back skin of mice, and the mice were treated with different methods to observe the healing process of the wound and study its influence on the wound healing. RESULTS The synthesized antimicrobial agent could be heated repeatedly without attenuation under near-infrared light, and could still reach a high temperature of 45 ℃ at a low concentration of 125 µg·mL^-1. At the same time, it could promote the release of loaded antibiotics, and the release rate reached 86%. Compared with 200 µg·mL^-1 solution obtained by physical mixing of polydopamine and ciprofloxacin, the synthesized antimicrobial agent combined with near-infrared light showed more excellent antibacterial ability, and the bacteriostatic rate against Escherichia coli and Staphylococcus aureus was 99.9%. Antimicrobial agents with concentrations of only 0.312 5 µg·mL^-1 and 1.25 µg·mL^-1 combined with near infrared light significantly inhibited the growth of Escherichia coli and Staphylococcus aureus. Through the mouse skin defect model infected by Staphylococcus aureus, it was proved that the synthetic antibacterial agent still had excellent antibacterial effect in practical application, and could accelerate the healing of infected wound. CONCLUSION The synthesized antimicrobial agents have excellent antibacterial effect in vitro, and still have good antibacterial effect and promote wound healing under the conservative power irradiation without causing skin damage in vivo.