Nanoparticulate ophthalmic drug delivery of norfloxacin to prevent ocular infection after cataract surgery: Evaluation in animal model

Abstract

Post cataract surgery, patients generally experience bacterial infection called endophthalmitis which is considered as potent blinding complication. This infection arises from the colonization of Staphylococcus epidermidis on the newly implanted lense. To overcome this problem, we developed nanoparticulate ophthalmic drug delivery of Norfloxacin to prevent ocular infection after cataract surgery. Sustained release Norfloxacin loaded polymeric nanoparticles were developed by high pressure homogenization method. The nanoparticles were characterized for particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency (EE), in vitro Norfloxacin release and surface characteristics using scanning electron microscopy (SEM). The optimized nanoparticulate formulation was further used for the development of thermoreversible ophthalmic gel using poloxamer polymer. The formulated ophthalmic gel was evaluated for gelation temperature, pH, bioadhesiveness, and in vitro corneal permeation study. The antibacterial efficacy testing of thermoreversible gel was assessed in animal model (rabbit) infected with Staphylococcus epidermidis. At the end of study period the inhibitory effect of thermoreversible gel was determined on test animals. The antibacterial effects were compared with control group and plain thermoreversible gel (without nanoparticle formulation). The optimized nanoparticulate formulation of Norfloxacin showed slow and gradual sustained release over the period of 72 hours, encapsulation efficiency of between 90.12 to 98.50%, particle size 95–210 nm, PDI 0.18 to 0.212 and zeta potential between 20 to 25 mV. The nanoparticles were found spherical and smooth in nature. The optimized formulation of nanoparticle was used in thermoreversible gel. The results obtained showed that the thermoreversible gel was clear and transparent (prime requirement for ophthalmic product) with high gelling capacity and moderately viscous liquid (1170 cp), highest bioadhesive strength of 2312.90 dyne/cm2. The exvivo corneal study showed excellent permeation through cornea as compare to control sample. Norfloxacin released from thermoreversible gel killed Staphylococcus epidermidis in animal models as compare to control group and showed effect up to 14 days. With these findings, we demonstrate a new and effective system for sustained drug release of Norfloxacin from thermoreversible gel with specific application to prevent ocular infection after cataract surgery.