Modeling, Optimization, and In Vitro Corneal Permeation of Chitosan-Lomefloxacin HCl Nanosuspension Intended for Ophthalmic Delivery

Abstract

Lomefloxacin HCl (LF) is a widely used fourth-generation fluoroquinolone antibiotic. Like most drug solutions administered via ocular route, it is usually eliminated by eye protective mechanisms. Chitosan (CS) is a natural polysaccharide polymer with numerous advantages in ocular delivery with, antibacterial, and antifungal properties. The aims were to formulate and optimize LF nanosuspensions (NS) with enhanced antimicrobial activity and prolonged duration using ionic gelation technique. Formulation variables included drug load, CS concentration, crosslinker type (tripolyphosphate and sodium alginate), and concentration. Nanosuspension properties (particle size, zeta potential, polydispersity index, entrapment efficiency, drug release, and permeation through bovine cornea) were evaluated. The artificial neural networks (ANNs) model showed optimum entrapment efficiency of 70.63 % w/w, particle size of 176 ± 0.28 nm, and zeta potential of 13.65 mV. Transmission electron microscopy illustrated the production of well-defined spherical nanoparticles. The nanosuspensions showed prolonged release of LF for more than 8 h and threefold increase in amount permeated through bovine cornea compared to drug solution. Improved antibacterial activity of the nanosuspension was noted where 2- and 3.5-fold decrease in minimum inhibitory concentration (MIC) of drug against Gram-positive and Gram-negative bacteria were observed, respectively. Twofold decrease in minimum bactericidal concentration (MBC) of drug nanosuspension against both types of bacteria was also demonstrated. Histopathological examination showed compatibility of optimized formulation with eye tissues in rabbit model. Therefore, model-optimized LF nanosuspension could be an ideal solution to ocular infections by virtue of their augmented activity, high compatibility, and improved permeability.