Formulation and Characterization of Stimuli-Responsive In Situ Gel For Treatment of Bacterial Keratitis

Abstract

Background: The aim of this study is to develop an in-situ gelling system for the effective delivery and sustainedrelease of levofloxacin in the treatment of anterior corneal infections.

Material and Methods: Sodium alginate (SA) and hydroxypropyl methylcellulose (HPMC) were used to formulate in-situ gels (ISGs) with formulation codes F1-F12 and 0.5% levofloxacin solution was used as a control. The formulations were evaluated for clarity, pH, gelling  capacity, drug content and antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Streptococcus pneumoniae and  Staphylococcus aureus using the KirbyBauer disk diffusion test. The irritability and toxicity of select formulations were assessed using the  Hen’s Egg Test, Chorioallantoic Membrane (HETCAM) assay.

Results: The formulated ISGs were within pH range of 5.86 and 7.60.  Formulation F7 (0.5% SA + 1.5% HPMC) had the highest gelling capacity and all ISGs had comparable activity against the tested  organisms. Formulation F6 (1% HPMC + 1% SA) had the slowest release with approximately 60% release after 4 h, formulation F11 (1.5%  HPMC + 2% SA) had the fastest release of 72% after 4 h while LVF solution (control) released 70% in 1 h. There was no significant (p =  0.101) change in the concentration of levofloxacin ISGs after storage at 25o C for 60 days and the HETCAM test confirmed the non-toxicity  and non-irritability of the formulations.

Conclusions: Levofloxacin in-situ gels formulated with SA and HPMC E5 LV are able to sustain the  release of levofloxacin for 8 h and retain their effectiveness against relevant ocular bacterial infections.