Rifampicin-loaded PLGA nanoparticles for local treatment of musculoskeletal infections: Formulation and characterization

Systemic treatment of orthopedic device-related infections requires potentially toxic doses to reach local therapeutic levels. A locally applied nanosized drug delivery system can provide a high drug dose at the target site. Branched PLGA of lower molar mass was used for rifampicin-loaded nanoparticles (RIF-NPs) formulation by the nanoprecipitation method. The formulation variables influenced the NPs size ranging from 200 to 380 nm. The missing peak of crystalline rifampicin on the DSC scan of the NPs indicates that the drug was molecularly dispersed. The negative charge of the NPs in the physiological buffer was masked by a nonionic surfactant or converted to a positive one by a cationic surfactant, which promotes bioadhesion, penetration, and antimicrobial effect of locally applied RIF-NPs without being toxic to proliferation. Low values of loading capacity showed that PLGA predominates in the NPs, which, however, perform their function as a drug carrier ensuring sustained RIF release. The ex vivo dissolution study of RIF-NPs impregnated into the cancellous allogeneic bone grafts showed a low initial burst followed by sustained release of RIF for 7 days. Rifampicin-loaded PLGA nanoparticles may contribute to the prevention of resistant biofilm formation in patients with implanted devices and the local treatment of infections in open musculoskeletal injuries. [Display omitted] •Rifampicin entrapped in biocompatible and biodegradable polymer.•Effective and safe local treatment of musculoskeletal infections.•Prevention of staphylococcal biofilm formation by a nanosized drug delivery system.•Adjustable size and surface charge of the NPs by formulation variables.•Prolonged release of incorporated rifampicin by linear kinetics.