Development and evaluation of cationic nanostructured lipid carriers for ophthalmic drug delivery of besifloxacin

Abstract Besifloxacin hydrochloride (BSF) is a new ophthalmic antibiotic. However, its low water solubility limits its therapeutic efficacy. This article reported a novel lipid based drug delivery system to enhance ocular bioavailability of BSF. Cationic nanostructured lipid carriers (CNLC) were prepared and optimized by Box-Behnken design via using Design Expert Software®. Effect of concentration of three independent variables, Stabilizer, Solid lipid and Liquid Lipid were studied on three dependent variables Particle size, Polydispersity Index (PDI) and zeta potential of the CNLC particles. The surfactant, hexadecyltrimethylammonium bromide (CTAB) was used to optimize the surface charge of the nano-particles. The BSF loaded nano-particles, CNLC-BSF, were characterized fully. Rhodamine was trapped into CNLC-BSF for imaging. The cytotoxicity and cellular infiltration of CNLC-BSF were assessed by 2-dimensional (2D) and 3-dimensional (3D) conjunctival tissue model. It was revealed that the CNLC's parameters, particle size, PDI and zeta potential, remained stable over 2-week storage period. The entrapment efficiency was around 80% for optimum formulation. The cell internalization of CNLC increased when CTAB concentration increased in CNLC-BSF. The formulation showed good penetration property through the 3D tissue model. The cytotoxicity assessed by MTT assay showed minimum 60% cell viability on conjunctival fibroblast model for the optimized formula with inclusion of 0.6 mg/mL BSF.