Sustained Delivery of Analgesic and Antimicrobial Agents to Knee Joint by Direct Injections of Electrosprayed Multipharmaceutical-Loaded Nano/Microparticles

In this study, we developed biodegradable lidocaine–/vancomycin–/ceftazidime–eluting poly(d,l–lactide–co–glycolide) (PLGA) nano/microparticulate carriers using an electrospraying process, and we evaluated the release behaviors of the carriers in knee joints. To prepare the particles, predetermined weight percentages of PLGA, vancomycin, ceftazidime, and lidocaine were dissolved in solvents. The PLGA/antibiotic/lidocaine solutions were then fed into a syringe for electrospraying. After electrospraying, the morphology of the sprayed nano/microparticles was elucidated by scanning electron microscopy (SEM). The in vitro antibiotic/analgesic release characteristics of the nano/microparticles were studied using high-performance liquid chromatography (HPLC). In addition, drug release to the synovial tissues and fluids was studied in vivo by injecting drug-loaded nano/microparticles into the knee joints of rabbits. The biodegradable electrosprayed nano/microparticles released high concentrations of vancomycin/ceftazidime (well above the minimum inhibition concentration) and lidocaine into the knee joints for more than 2 weeks and for over 3 days, respectively. Such results suggest that electrosprayed biodegradable nano/microcarriers could be used for the long-term local delivery of various pharmaceuticals.