Diflunisal-loaded poly(propylene sulfide) nanoparticles decrease S. aureus-mediated bone destruction during osteomyelitis.

Abstract

Osteomyelitis is a debilitating infection of bone that results in substantial morbidity. Staphylococcus aureus is the most commonly isolated pathogen causing bone infections and features an arsenal of virulence factors that contribute to bone destruction and counteract immune responses. We previously demonstrated that diflunisal, a nonsteroidal anti-inflammatory drug, decreases S. aureus-induced bone destruction during osteomyelitis when delivered locally from a resorbable drug delivery depot. However, local diflunisal therapy was complicated by bacterial colonization of the depot's surface, highlighting a common pitfall of devices for local drug delivery to infected tissue. It is, therefore, critical to develop an alternative drug delivery method for diflunisal to successfully repurpose this drug as an antivirulence therapy for osteomyelitis. We hypothesized that a nanoparticle-based parenteral delivery strategy would provide a method for delivering diflunisal to infected tissue while circumventing the complications associated with local delivery. In this study, we demonstrate that poly(propylene sulfide) (PPS) nanoparticles accumulate at the infectious focus in a murine model of staphylococcal osteomyelitis and are capable of efficaciously delivering diflunisal to infected bone. Moreover, diflunisal-loaded PPS nanoparticles effectively decrease S. aureus-mediated bone destruction, establishing the feasibility of systemic delivery of an antivirulence compound to mitigate bone pathology during osteomyelitis.

• Authors: Caleb A Ford, Thomas J Spoonmore, Mukesh K Gupta, Craig L Duvall, Scott A Guelcher, James E Cassat
• Journal: Journal of orthopaedic research : official publication of the Orthopaedic Research Society (J Orthop Res) Vol. 39 Issue 2 Pg. 426-437 (02 2021) ISSN: 1554-527X [Electronic] United States
• PMID: 33300149 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Orthopaedic Research published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Polymers
• Sulfides
• poly(propylene sulfide)
• Diflunisal

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage)
• Bone and Bones (drug effects)
• Cell Line
• Diflunisal (administration & dosage)
• Drug Delivery Systems
• Drug Evaluation, Preclinical
• Female
• Host-Pathogen Interactions (drug effects)
• Mice
• Nanoparticles (chemistry)
• Osteomyelitis (drug therapy)
• Polymers
• Staphylococcal Infections (drug therapy)
• Staphylococcus aureus
• Sulfides