title: Fusidic acid and rifampicin co-loaded PLGA nanofibers for the prevention of orthopedic implant associated infections.
abstract: 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.
authors: Faculty of Pharmaceutical Science, The University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors: Samuel E
authors: SE
authors: Gilchrist
authors: Dirk
authors: D
authors: Lange
authors: Kevin
authors: K
authors: Letchford
authors: Horacio
authors: H
authors: Bach
authors: Ladan
authors: L
authors: Fazli
authors: Helen M
authors: HM
authors: Burt
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D019643:Arthroplasty, Replacement; D001424:Bacterial Infections / Q000188:drug therapy / Q000517:prevention & control*; D016503:Drug Delivery Systems; D005260:Female; D005672:Fusidic Acid / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D057139:Nanofibers / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D019736:Prostheses and Implants / Q000009:adverse effects; D016459:Prosthesis-Related Infections / Q000188:drug therapy / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000008:administration & dosage* / Q000737:chemistry; D013212:Staphylococcus epidermidis / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005672:Fusidic Acid; D012293:Rifampin