Carboxylated nanofibrillated cellulose empowers moxifloxacin to overcome Staphylococcus aureus biofilm in bacterial keratitis

Abstract

Bacterial keratitis is one of the vision-threatening ocular diseases that is increasing at an alarming rate due to antimicrobial resistance. One of the primary causes of antimicrobial resistance could be biofilm formation, which alters the mechanism and physiology of the microorganisms. Even a potent drug fails to inhibit biofilm due to the extracellular polysaccharide matrix surrounding the bacteria, inhibiting the permeation of drugs. Therefore, we aimed to develop carboxylated nanocellulose fibers loaded with moxifloxacin (Mox-cNFC) as a novel drug delivery system to treat bacterial corneal infection. Nanocellulose fibers were fabricated using a two-step method involving citric acid hydrolysis followed by TEMPO oxidation to introduce carboxylated groups (1.12 mmol/g). The Mox-cNFC particles showed controlled drug release till 40 h through diffusion. In vitro biofilm inhibition studies showed the particle's ability to disrupt the biofilm matrix and enhance the drug penetration to achieve optimal concentrations that inhibit the persister cells (without increasing minimum inhibitory concentration), thereby reducing the bacterial drug-resistant property. In vivo studies revealed the therapeutic potential of Mox-cNFC to treat Staphylococcus aureus-induced bacterial keratitis with once-a-day treatment, unlike neat moxifloxacin. Mox-cNFC could improve patient compliance by reducing the frequency of instillation and a controlled drug release to prevent toxicity.