Development of Chitosan/Cyclodextrin Nanospheres for Levofloxacin Ocular Delivery

Abstract

Levofloxacin (LVF) is an antibacterial drug approved for the treatment of ocular infections. However, due to the low ocular bioavailability, high doses are needed, causing bacterial resistance. Polymeric nanospheres (NPs) loading antibiotic drugs represent the most promising approach to eradicate ocular infections and to treat pathogen resistance. In this study, we have developed chitosan NPs based on sulfobutyl-ether-β-cyclodextrin (CH/SBE-β-CD NPs) for ocular delivery of LVF. CH/SBE-β-CD NPs loading LVF were characterized in terms of encapsulation parameters, morphology, and sizes, in comparison to NPs produced without the macrocycle. Nuclear magnetic resonance and UV–vis spectroscopy studies demonstrated that SBE-β-CD is able to complex LVF and to influence encapsulation parameters of NPs, producing high encapsulation efficiency and LVF loading. The NPs were homogenous in size, with a hydrodynamic radius between 80 and 170 nm and positive zeta potential (ζ) values. This surface property could promote the interaction of NPs with the negatively charged ocular tissue, increasing their residence time and, consequently, LVF efficacy. In vitro, antibacterial activity against Gram-positive and Gram-negative bacteria showed a double higher activity of CH/SBE-β-CD NPs loading LVF compared to the free drug, suggesting that chitosan NPs based on SBE-β-CD could be a useful system for the treatment of ocular infections.

The Expanded Role of Chitosan in Localized Antimicrobial Therapy

“…Ocular bacterial infections, including keratitis, conjunctivitis, blepharitis, endophthalmitis, dacryocystitis, and orbital cellulitis, are exciting targets to explore the extended role of chitosan as an active pharmaceutical ingredient. Common causes of infections comprise S. aureus, coagulase-negative Staphylococcus, P. aeruginosa, Streptococcus pneumonia, E. coli, and Serratia species [328]. However, successful localized therapy is highly dependent on the performance of the drug vehicle-delivery system.…”

“…Chitosan was often studied in combination with other pharmaceutical excipients; for example, chitosan/cyclodextrin nanospheres were evaluated in vitro for their potential to improve the delivery of levofloxacin, a third-generation tricyclic quinolone. Novel NPs exhibited 2-fold increased antibacterial activity against both Gram-positive and Gramnegative bacteria compared with the free drug [328]. Sustained release of levofloxacin was also achieved utilizing thermosensitive chitosan-based hydrogel targeting postoperative endophthalmitis.…”

Advances in Nanostructures for Antimicrobial Therapy

“…Such submicrocarriers have the potential to be used as a drug delivery system for the treatment of respiratory extracellular infection with P. aeruginosa and/or S. aureus [ 180 ]. CS NPs based on sulfobutyl-ether-β-CD with sizes 80 and 170 nm and a positive zeta potential loaded with levofloxacin (LEV) exhibited 2-fold higher antibacterial activity against both Gram-positive and Gram-negative bacteria, suggesting their suitability for ocular delivery of the antibiotic to treat ocular infections [ 181 ].…”

Development of Chitosan–Tripolyphosphate Nanoparticles as Glycopeptide Antibiotic Reservoirs and Ex vivo Evaluation for Their Potential to Enhance the Corneal Permeation in Ocular Drug Delivery

“…52 An enhanced in vitro antibacterial activity was reported by levofloxacin ocular nanospheres in another study. 53 Abruzzo et al deigned VAN-loaded nanoparticles for ocular delivery in 2021, that indicated antibacterial efficacy and enhanced diffusion through the mucus layer of the eye. 54…”