Posterior Segment Ophthalmic Drug Delivery: Role of Muco-Adhesion with a Special Focus on Chitosan

Posterior segment eye diseases (PSEDs) including age macular degeneration (AMD) and diabetic retinopathy (DR) are amongst the major causes of irreversible blindness worldwide. Due to the numerous barriers encountered, highly invasive intravitreal (IVT) injections represent the primary route to deliver drugs to the posterior eye tissues. Thus, the potential of a more patient friendly topical route has been widely investigated. Mucoadhesive formulations can decrease precorneal clearance while prolonging precorneal residence. Thus, they are expected to enhance the chances of adherence to corneal and conjunctival surfaces and as such, enable increased delivery to the posterior eye segment. Among the mucoadhesive polymers available, chitosan is the most widely explored due to its outstanding mucoadhesive characteristics. In this review, the major PSEDs, their treatments, barriers to topical delivery, and routes of topical drug absorption to the posterior eye are presented. To enable the successful design of mucoadhesive ophthalmic drug delivery systems (DDSs), an overview of mucoadhesion, its theory, characterization, and considerations for ocular mucoadhesion is given. Furthermore, chitosan-based DDs that have been explored to promote topical drug delivery to the posterior eye segment are reviewed. Finally, challenges of successful preclinical to clinical translation of these DDSs for posterior eye drug delivery are discussed.

Gel-Based Materials for Ophthalmic Drug Delivery

The most common route of administration of ophthalmic drugs is the topical route because it is convenient, non-invasive, and accessible to all patients. Unfortunately, drugs administered topically are not able to reach effective concentrations. Moreover, their bioavailability must be improved to decrease the frequency of administrations and their side effects, and to increase their therapeutic efficiency. For this purpose, in recent decades, particular attention has been given to the possibility of developing prolonged-release forms that are able to increase the precorneal residence time and decrease the loss of the drug due to tearing. Among these forms, gel-based materials have been studied as an ideal delivery system because they are an extremely versatile class with numerous prospective applications in ophthalmology. These materials are used in gel eye drops, in situ gelling formulations, intravitreal injections, and therapeutic contact lenses. This review is intended to describe gel-based materials and their main applications in ophthalmology.

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

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.