Abstract
Purpose :
Antibiotic-loaded ocular drug delivey systems can potentially address challenges in topical drug administration. The aim of this in vitro study was to develop a an ocular insert of levofloxacin (LFX) wich would maintain effective drug concentration of the eye for prolonged periods of time.
Methods :
Each layer of the insert was produced by a refined solvent-casting method, out of 0.5% LFX solutions. The soluble layer was made of hypromellose (5%), sodium alginate (3%), gelatin (1%), and PEG400 (10%), while the bioerodible included chitosan (2%) and PEG400 (10%). Both formulations were characterised separately and after coupling. Physical and mechanical properties were tested. Uniformity of LFX content and release profile were assessed by validated analytical method. The extent of inserts antimicrobial efficacy was evaluated by growth dynamics of Staphylococcus aureus and Pseudomonas aeruginosa after exposure to LFX fractions released over time. Transepithelial drug permeability was assessed with an in vitro eye model, based on human epithelial corneal cell line culture.
Results :
The bilayered formulation resulted in inserts holding good physical and mechanical properties. Inserts mass (18.3 ± 0.4 mg), thickness (229 ± 4 µm) and LFX content (586.2 ± 6.7 µg) were found consistent, showing reduced variability. Suitability to manipulation could be inferred from inserts elasticity (elongation at max load 70.7 ± 9.7%) and flexibility (foldability > 300 times). The release pattern showed that one-third of LFX was released in the first 30 minutes, indicating immediate effectiveness of inserts against bacteria. The remaining LFX fractions were progressively released in 24 hours, and they appeared appropriate to inhibit Staphylococcus aureus and Pseudomonas aeruginosa during kinetic growth assays. The bilayered inserts exhibited a linear permeability profile of LFX through the epithelial tissue.
Conclusions :
The new bilayered LFX-loaded insert showed good physical and mechanical properties, indicating suitability for ocular administration. Extended antimicrobial efficacy was demonstrated by drug content and release profile, and confirmed by bacterial growth inhibition. Transepithelial drug permeabilty was found constant and incomplete, suggesting furtherly extended efficacy of the insert.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.