Ophthalmologic infections can be challenging to treat because of the relative impermeability of the cornea. It is estimated that only 1% to 5% of the applied topical antibiotic penetrates into the intraocular zone.1,2 Levofloxacin is a broad-spectrum antibiotic with excellent antibacterial activity on the cornea and conjunctiva.3 However, optimizing drug delivery and increasing levofloxacin bioavailability have been a challenge. Several delivery systems developed in recent years included levofloxacin-loaded formulations using different polymers such as nanoparticles, nanoparticle-laden in situ gel, and nanohydrogels.4-6 These formulations have not been optimized because of their non-mucoadhesive nature, drug absorption characteristics, and low drug loading and encapsulation.
Researchers from India and the Kingdom of Saudi Arabia recently published an article on the use of nanoparticle in situ gel combination to increase the availability of levofloxacin at the corneal surface.7 In their experiments, Ameeduzzafar and colleagues used chitosan nanoparticles to encapsulate levofloxacin. Chitosan is a naturally-occurring polycationic hydrophilic polymer that is widely used in ophthalmic formulations.8 It has bioadhesive characteristics, permeability-enhancing properties and antibacterial activity.9
Chitosan nanoparticles were prepared by ionic gelation method using chitosan and sodium tripolyphosphate. Various formulations were evaluated for physicochemical parameters. The optimized formulation was converted into a liquid form that changes into a gel form once in contact with the eye (‘sol-gel’ system). This increases corneal residence time and improves drug surface retention. The formulations showed the particle size in nanometric range with high levofloxacin drug loading and entrapment efficiency.
The antimicrobial property of the levofloxacin-chitosan nanoparticle in situ gel was compared with levofloxacin solution using nutrient agar media with the cup-plate method. The novel formulation demonstrated higher antibacterial activity against P. aeruginosa and S. aureus. Pharmacoscintigraphic study revealed reduced corneal clearance, naso-lachrymal drainage and higher retention of levofloxacin compared with levofloxacin solution. The optimized formulation was found to be non-irritating and safe for topical ophthalmic use as assessed by the HET-CAM test and goat corneal histopathologic examination. The shelf life of the formulation is approximately two years.
The results of the study demonstrated that the levofloxacin-loaded chitosan nanoparticles in situ gel system is an efficient carrierfor ocular delivery of levofloxacin. This is a promising formulation that has not only enhanced corneal residence time, but has also improved antimicrobial activity against P. aeruginosa and S. aureaus.
PMID: 29199125 (Ameeduzzafar et al. Int J Biol Macromol. 2018 Mar;108:650-659)