Title : Release and activity of the broad spectrum antibiotic Rifampicin from biodegradable polymer PLGA
Abstract:
Medical device infection is one of the most problematic issues associated with implanted medical devices. More than 60% of nosocomial infections are related to a medical device, with treatment being particularly challenging. Pathogenesis of infection frequently involves formation of a protective polysaccharide matrix, known as a biofilm, which acts as a barrier to both host immune response and administered antimicrobials. In order to eradicate a biofilm a significantly higher dose of antimicrobial is required when compared to the planktonic form of the same microorganism. Delivering an effective dose to the site of infection with systemic methods is extremely problematic and often cannot be achieved, meaning explant and replacement of a medical device is the only option. However these procedures are often contraindicated or high risk, with no guarantee that re-infection will not occur. As the most common causative microorganisms are Staphylococcal species, it is believed that initial contamination occurs during implantation. It is therefore desirable that for a time after implantation, during which there is a higher risk of infection, a medical device be resistant to infection pathogenesis.
Drug-eluting technology using a biodegradable polymer, similar to that already in use in some drug-eluting stents, may be of use in certain medical devices as a means of achieving such infection prevention. To investigate this, the polymer poly(D,L-lactic-co-glycolic acid) (PLGA) was formulated with the broad spectrum antibiotic rifampicin, and over 10 weeks both the release and antimicrobial activity against Staphylococcus aureus biofilm formation examined. The release study revealed that rifampicin can readily be released from PLGA, and that release is highly tunable by altering the ratio of polymer to drug. Ratios examined were PLGA:rifampicin 50:50 and 60:40, this small change in ratio produced two alternative release profiles with significantly different percentage release. However, both the 50:50 and the 60:40 PLGA:rifampicin formulations released the majority (>90%) of their respective rifampicin loads during the initial 4 weeks of release. Despite this the biofilm inhibition study, which used implantable medical grade polyester, proved the potency of rifampicin by revealing extended activity against S. aureus biofilm formation. After 10 weeks of rifampicin release the results showed a 99% and 90% reduction in biofilm formation when compared to material coated with PLGA alone.
What this study has demonstrated is that biodegradable polymer drug delivery technology can be used to control release of an antimicrobial, and that the antimicrobial activity can be retained for an extended period of time (≥10 weeks). This technology may therefore be of potential utility to prevention of infection in implanted medical devices.
Audience take away:
• The potential for biodegradable polymers to be used as a drug delivery method for antimicrobials
• Antimicrobial activity can be retained for an extended period of time by using a biodegradable polymer to control release
• Demonstrated proof of principle, which may help inform future studies
