Daniel Matija, Chessman Robert, Al-Zahid Saif, Richards Brian, Rahman Cheryl, Ashraf Waheed, McLaren Jane, Cox Helen, Qutachi Omar, Fortnum Heather, Fergie Neil, Shakesheff Kevin, Birchall John P, Bayston Roger R
Department of Otorhinolaryngology–Head and Neck Surgery, The University of Nottingham, Queens Medical Centre, Derby Road, Nottingham NG7 2UH, England.
Arch Otolaryngol Head Neck Surg. 2012 Oct;138(10):942-9. doi: 10.1001/archotol.2013.238.
To develop a biodegradable, modified-release antibiotic pellet capable of eradicating biofilms as a potential novel treatment for biofilm infections.
Pellets containing poly(DL-lactic-co-glycolic acid) microparticles, rifampin and clindamycin hydrochloride (3.5%, 7%, or 28% antibiotic by weight), and carrier gel (carboxymethylcellulose or poloxamer 407) were tested in vitro. Drug release was assessed using serial plate transfer testing and high-performance liquid chromatography, and pellets were tested against biofilms in an in vitro model of Staphylococcus aureus biofilm grown on silicone.
Serial plate transfer testing demonstrated continuing bacterial inhibition for up to 21 days for all pellets studied. High-performance liquid chromatography showed high levels of drug release for 2 to 4 days, with greatly reduced levels subsequently; continued measurable clindamycin (but not rifampin) release for up to 21 days was achieved. Pellets made with poloxamer released higher drug levels for a longer period. Irrespective of the carrier gel used, pellets containing 7% and 28% (but not 3.5%) antibiotic eradicated biofilms successfully.
Antibiotic pellets can release antibiotics for up to 21 days and are able to eradicate biofilms in an in vitro model. Use of modified-release antibiotic formulations in the middle ear as a treatment for biofilms appears to be a potentially promising new therapy for otitis media with effusion.
开发一种可生物降解的缓释抗生素微丸,作为生物膜感染的潜在新型治疗方法,能够根除生物膜。
对含有聚(DL-乳酸-乙醇酸共聚物)微粒、利福平及盐酸克林霉素(按重量计抗生素含量为3.5%、7%或28%)和载体凝胶(羧甲基纤维素或泊洛沙姆407)的微丸进行体外测试。使用连续平板转移试验和高效液相色谱法评估药物释放情况,并在硅胶上生长的金黄色葡萄球菌生物膜体外模型中对微丸进行生物膜测试。
连续平板转移试验表明,所研究的所有微丸对细菌的抑制作用可持续长达21天。高效液相色谱显示,药物在2至4天内有高水平释放,随后水平大幅降低;实现了克林霉素(而非利福平)长达21天的持续可测释放。用泊洛沙姆制成的微丸在较长时间内释放更高水平的药物。无论使用何种载体凝胶,含7%和28%(而非3.5%)抗生素的微丸均成功根除了生物膜。
抗生素微丸可释放抗生素长达21天,并能够在体外模型中根除生物膜。在中耳使用缓释抗生素制剂作为生物膜的治疗方法,似乎是治疗渗出性中耳炎一种潜在的有前景的新疗法。