Antimicrobial activity and biocompatibility of slow-release hyaluronic acid-antibiotic conjugated particles.

Abstract

Here, the aim was to design and use a long-lasting antibiotic release system for prevention of postoperative infections in ophthalmic surgery. Ciprofloxacin and vancomycin-conjugated hyaluronic acid (HA) particles were prepared as drug carriers for sustained release of antibiotics. The antimicrobial effects of the released drugs were determined by disc-diffusion and macro-dilution tests at different times up to 2weeks. Slow degradable HA particles were obtained with 35.2wt% degradation within 21days. The drug loading amount was increased by employing two sequential chemical linking (conjugation, 2C) and one physical absorption loading (A) procedures (2C+A processes) from 148±8 to 355±11mg/g HA particles for vancomycin. The amounts of vancomycin and ciprofloxacin that were released linearly was estimated as 64.35±7.35 and 25.00±0.68mg/g, respectively, from drug-conjugated HA particles in 100h. Antimicrobial studies revealed that antibiotic-conjugated HA particles could inhibit the growth of microorganisms from 1h to 1week. The MBC values were measured as 0.25, 4.0, and 0.25mg/mL against Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis, respectively, after 72h incubation time. Cytotoxicity studies showed no difference between fibroblast growth or corneal thickness after 5days with or without HA-antibiotic particles. The drug release studies and antimicrobial activity of antibiotic-loaded HA particles with time against various bacteria further revealed that HA particles are very effective in preventing bacterial infections. Likewise, cytotoxicity studies suggest that these particles pose no toxicity to eukaryotic cells, including corneal endothelium.