Fusidic acid and rifampicin co-loaded PLGA nanofibers for the prevention of orthopedic implant associated infections

• Published in: Journal of controlled release Vol. 170; no. 1; pp. 64 - 73
• Main Authors: Gilchrist, Samuel E., Lange, Dirk, Letchford, Kevin, Bach, Horacio, Fazli, Ladan, Burt, Helen M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 28.08.2013
• Subjects: Animal models; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; anti-infective properties; antibiotic resistance; Arthroplasty, Replacement; Bacterial Infections - drug therapy; Bacterial Infections - prevention & control; biodegradability; Controlled drug delivery; Drug Delivery Systems; drugs; Electrospinning; encapsulation; Female; Fusidic acid; Fusidic Acid - administration & dosage; Fusidic Acid - chemistry; Lactic Acid - chemistry; methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Microbial Sensitivity Tests; microorganisms; Nanofibers; Nanofibers - administration & dosage; Nanofibers - chemistry; orthopedics; Polyglycolic Acid - chemistry; prostheses; Prostheses and Implants - adverse effects; Prosthesis-Related Infections - drug therapy; Prosthesis-Related Infections - prevention & control; Rats; Rats, Sprague-Dawley; Rifampicin; Rifampin - administration & dosage; Rifampin - chemistry; sodium; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus epidermidis - drug effects; surgery; titanium; Fusidic acid; Electrospinning; Controlled drug delivery; Rifampicin; Nanofibers
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2013.04.012

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. [Display omitted]