Kuming General Hospital of Chengdu Military Region, Kuming, Yunnan, China 650032.
Drug Dev Ind Pharm. 2012 Nov;38(11):1298-304. doi: 10.3109/03639045.2011.648196. Epub 2012 Jan 19.
In the current study, nano-hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) ceramics scaffolds loaded with cationic liposomal ceftazidime (CLCs) prepared by modified reverse phase evaporation method, the investigations of their release characteristics were performed by the dissolution tests, in vitro anti-biofilm activity of the scaffolds was studied by the determination of bacterial susceptibility with ELISA. The mean particle size, zeta potential, pH and entrapment efficiency of the CLCs studied were 161.5 ± 5.37 nm, 60.60 ± 5.24 mV, 6.90 ± 0.07 and 16.57 ± 0.13%, respectively. Electron microscopic images of the samples indicated that the liposomes were well preserved in the scaffolds and that it was the CLCs rather than free ceftazidime releasing from the scaffolds. The minimal inhibitory concentrations (MICs) to Staphylococcus aureus of free ceftazidime and its liposomal formulation were 6.00 μg/mL and the release behaviors of both CLCs and free ceftazidime from scaffolds were based on the dissolution/diffusion processes, Fick's law. These results demonstrated that CLCs could inhibit remarkably the formation of S. aureus biofilm more effectively than free ceftazidime (P < 0.05). The study demonstrated that the HA/β-TCP ceramic scaffolds was such a material that could sustain release CLCs and maintain the adequate amounts of CLCs to absorb to biofilm. It provided an ideal way to inhibit bacterial biofilms for clinical practices.
在本研究中,通过改良的反相蒸发法制备载阳离子脂质体头孢他啶(CLCs)的纳米羟基磷灰石/β-磷酸三钙(HA/β-TCP)陶瓷支架,通过溶解试验研究了它们的释放特性,通过 ELISA 测定细菌敏感性研究了支架的体外抗生物膜活性。研究的 CLCs 的平均粒径、zeta 电位、pH 值和包封效率分别为 161.5 ± 5.37nm、60.60 ± 5.24mV、6.90 ± 0.07 和 16.57 ± 0.13%。样品的电子显微镜图像表明,脂质体在支架中得到了很好的保存,并且是 CLCs 而不是游离头孢他啶从支架中释放出来。游离头孢他啶和其脂质体制剂对金黄色葡萄球菌的最小抑菌浓度(MICs)分别为 6.00μg/mL,CLC 和游离头孢他啶从支架中的释放行为均基于溶解/扩散过程,符合菲克定律。这些结果表明,CLCs 比游离头孢他啶更能显著抑制金黄色葡萄球菌生物膜的形成(P < 0.05)。研究表明,HA/β-TCP 陶瓷支架是一种能够持续释放 CLCs 并保持足够数量的 CLCs 吸收生物膜的材料。它为临床实践中抑制细菌生物膜提供了一种理想的方法。