Purpose: Formulation of new drug delivery system as Natamycin (NT)-loaded nanoparticle niosomal formulae mixed in different polymer gel, with the addition of ketorolac tromethamine (KETR). Pharmaceutical and experimental assessments to evaluate their safety and efficacy in treating Aspergillus keratitis. Methods: NT nanoparticle niosomes prepared by reverse-phase evaporation technique were mixed in different polymers, with the addition of KETR. Two formulae are evaluated in this study: F1 [NT-loaded nanoparticle niosomes/0.5% KETR 4% carboxymethyl cellulose (Na.CMC) gel], F2 [NT-loaded nanoparticle niosomes/0.5% KETR 2% hydroxypropylmethyl cellulose (HPMC)-E4 gel], and mixed marketed products (MMP), namely Natamet® and Ketoroline® suspension eye drops. NT-loaded nanoparticle niosomes/0.5% KETR were evaluated through viscosity determination, mucoadhesive attractive force, and in vitro NT release studies. The in vivo antifungal evaluation was performed on 45 albino rabbits, Aspergillus species were inoculated in right corneas of all rabbits, and then rabbits were subdivided into 3 groups, 15 rabbits each: Group A: received F1, Group B: received F2, and Group C: received MMP. Daily examination of rabbits was performed for evaluation of corneal infiltration, and signs of iritis. Two weeks later, rabbits were euthanized; their corneas were dissected at the limbus and sent for histopathological evaluation. Results: F1 had a higher viscosity and more mucoadhesive power than F2, and showed better results on corneal infiltration, and level of hypopyon. These results were consistent with the histopathological examination. Conclusion: The formula of NT-loaded nanoparticle niosomes/0.5% KT 4% Na.CMC gel has the best results from all pharmaceutical in vitro evaluations and a better cure percent in experimental application.
Keywords: Aspergillus; Natamycin; fungal keratitis; niosomes.