Faculty of Pharmaceutical Science, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
J Control Release. 2013 Aug 28;170(1):64-73. doi: 10.1016/j.jconrel.2013.04.012. Epub 2013 Apr 30.
Implant-associated infections following invasive orthopedic surgery are a major clinical problem, and are one of the primary causes of joint failure following total joint arthroplasty. Current strategies using perioperative antibiotics have been met with little clinical success and have resulted in various systemic toxicities and the promotion of antibiotic resistant microorganisms. Here we report the development of a biodegradable localized delivery system using poly(D,L-lactic acid-co-glycolic acid) (PLGA) for the combinatorial release of fusidic acid (FA) (or its sodium salt; SF) and rifampicin (RIF) using electrospinning. The drug-loaded formulations showed good antibiotic encapsulation (~75%-100%), and a biphasic drug release profile. All dual-loaded formulations showed direct antimicrobial activity in vitro against Staphylococcus epidermidis, and two strains of methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, lead formulations containing 10% (w/w) FA/SF and 5% (w/w) RIF were able to prevent the adherence of MRSA to a titanium implant in an in vivo rodent model of subcutaneous implant-associated infection.
骨科手术相关的植入物感染是一个主要的临床问题，也是全膝关节置换术后关节失败的主要原因之一。目前使用围手术期抗生素的策略临床效果甚微，且导致了各种全身毒性和抗生素耐药微生物的出现。在这里，我们报告了一种使用聚（D，L-乳酸-co-乙醇酸）（PLGA）的可生物降解局部递药系统的发展，该系统可通过静电纺丝联合释放夫西地酸（FA）（或其钠盐 SF）和利福平（RIF）。载药配方显示出良好的抗生素包封率（约 75%-100%）和双相药物释放特征。所有双载药配方均显示出对表皮葡萄球菌和两种耐甲氧西林金黄色葡萄球菌（MRSA）的体外直接抗菌活性。此外，含有 10%（w/w）FA/SF 和 5%（w/w）RIF 的主导配方能够防止 MRSA 在皮下植入物相关感染的体内啮齿动物模型中黏附在钛植入物上。
