Abstract
Objective: This study aimed to optimize and evaluate the controlled release rate, ocular irritancy, and in vitro antimicrobial properties of levofloxacinentrapped in the epichlorohydrin-crosslinked hydrogel of sodium carboxymethyl cellulose (NaCMC) and gelatin.Materials and Methods: Various parameters such as polymer ratio, amount of crosslinker, temperature, reaction time, swelling capacity, and percentdrug loading were considered in Optimized levofloxacin hydrogel. Hydrogel preparations with higher amount of drug loaded were further analyzedto determine its in vitro drug release rate, ocular irritancy on New Zealand rabbits, and antimicrobial activities against Pseudomonas aeruginosaand Staphylococcus aureus. Optimized levofloxacin hydrogel (OLH) was then subjected to 3-month stability testing at 40 ± 2°C and 75 ± 5% relativehumidity in which samples were withdrawn at the end of each month for analysis.Results: Polymer groups with higher concentrations of NaCMC have higher swelling and drug loading capacities than those with higher gelatinconcentrations. Meanwhile, qualitative analysis using differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanningelectron microscopy verified the presence of levofloxacin in the epichlorohydrin-cross-linked hydrogel. Among the four polymer ratio, F3 was theoptimized hydrogel with drug-loaded concentration of 99.50%, which was within the acceptable assay limit of 0.5% levofloxacin solution based onUnited States Pharmacopeia monograph. It followed the Higuchi kinetic model with a drug release mechanism of super case 2 transport indicatinghydrogel swelling as a key factor for its controlled drug release. In vitro, antibacterial test against P. aeruginosa and S. aureus was sensitive to optimizedlevofloxacin hydrogel (OLH) with inhibitory diameter zones of 31.68 and 37.05 mm, respectively. Ocular irritancy test also showed that the OLH isnon-irritating on installation in the cul-de-sac of New Zealand rabbits.Conclusion: Optimized levofloxacin hydrogel was effective, non-irritating, and stable, which can be used as an alternative to conventional 0.5%levofloxacin ophthalmic solution.
Highlights
Misuse and overuse of antimicrobials impair their abilities to treat infections
Qualitative analysis using differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy verified the presence of levofloxacin in the epichlorohydrin-cross-linked hydrogel
Antibacterial test against P. aeruginosa and S. aureus was sensitive to optimized levofloxacin hydrogel (OLH) with inhibitory diameter zones of 31.68 and 37.05 mm, respectively
Summary
Misuse and overuse of antimicrobials impair their abilities to treat infections. It can prolong illnesses which may lead to disabilities and deaths. Eye infections such as bacterial and fungal keratitis are one of the major causes of ophthalmic morbidities and visual loss with a reported incidence of 17–36% worldwide [1] It is a second predisposing factor of corneal opacifications which is commonly associated with soft contact lens users with a reported annual ulcerative keratitis incidence of 4–21/10,000 daily and extended wear users [2]. Levofloxacin, a fourth-generation fluoroquinolone and an active L-isomer of Ofloxacin, is proven safe in treating bacterial conjunctivitis, keratitis, and other eye infections with known mechanism of inhibiting DNA gyrase and topoisomerase IV which are important steps for bacterial DNA metabolism [4] It is registered as Quixin® (US), Oftaquix® (Europe), and Cravit® (Japan) with disadvantages similar to conventional eye preparations, such as rapid tear turnover and drug impermeability to corneal epithelium membranes similar to other conventional eye drops. Patient non-compliance is an issue due to high frequencies of eye drop installations, which is a contributory factor to microbial resistance aside from improper dosage regimen, misuse, and overuse of topical antibacterial and extended duration of therapy
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