Degradable and Non-Degradable Chondroitin Sulfate Particles with the Controlled Antibiotic Release for Bacterial Infections


Creative Commons License

Suner S. S. , ŞAHİNER M., Ayyala R. S. , ŞAHİNER N.

PHARMACEUTICS, vol.14, no.8, 2022 (Peer-Reviewed Journal) identifier identifier

  • Publication Type: Article / Article
  • Volume: 14 Issue: 8
  • Publication Date: 2022
  • Doi Number: 10.3390/pharmaceutics14081739
  • Journal Name: PHARMACEUTICS
  • Journal Indexes: Science Citation Index Expanded, Scopus, Academic Search Premier, BIOSIS, EMBASE, Directory of Open Access Journals
  • Keywords: chondroitin sulfate, CS microgels, nanogels, controlled degradation, drug delivery, tobramycin, amikacin, Pseudomonas keratitis, POLYMERIC NANOPARTICLES, OCULAR DELIVERY, TOBRAMYCIN, MICROPARTICLES, FORMULATION, KERATITIS

Abstract

Non-degradable, slightly degradable, and completely degradable micro/nanoparticles derived from chondroitin sulfate (CS) were synthesized through crosslinking reactions at 50%, 40%, and 20% mole ratios, respectively. The CS particles with a 20% crosslinking ratio show total degradation within 48 h, whereas 50% CS particles were highly stable for up to 240 h with only 7.0 +/- 2.8% weight loss in physiological conditions (pH 7.4, 37 degrees C). Tobramycin and amikacin antibiotics were encapsulated into non-degradable CS particles with high loading at 250 g/mg for the treatment of corneal bacterial ulcers. The highest release capacity of 92 +/- 2% was obtained for CS-Amikacin particles with sustainable and long-term release profiles. The antibacterial effects of CS particles loaded with 2.5 mg of antibiotic continued to render a prolonged release time of 240 h with 24 +/- 2 mm inhibition zones against Pseudomonas aeruginosa. Furthermore, as a carrier, CS particles significantly improved the compatibility of the antibiotics even at high particle concentrations of 1000 g/mL with a minimum of 71 +/- 7% fibroblast cell viability. In summary, the sustainable delivery of antibiotics and long-term treatment of bacterial keratitis were shown to be afforded by the design of tunable degradation ability of CS particles with improved biocompatibility for the encapsulated drugs.