Potential chitosan-coated alginate nanoparticles for ocular delivery of daptomycin

Abstract

Daptomycin may offer an antibacterial alternative for the treatment of endophthalmitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and other potential agents. In the present project, mucoadhesive chitosan-coated alginate (CS-ALG) nanoparticles are proposed as an effective delivery system for daptomycin permeation across ocular epithelia, with potential for the treatment of bacterial endophthalmitis. CS-ALG nanoparticles were prepared by ionotropic pre-gelation of an alginate core followed by chitosan polyelectrolyte complexation, and characterized regarding particle size, polydispersity, and zeta potential. The encapsulation efficiency was determined and antimicrobial activity was also tested after encapsulation of the antibiotic. Also, in vitro ocular permeability of free daptomycin and encapsulation into chitosan and CS-ALG nanoparticles was evaluated using ocular epithelial cell culture models. Formulated daptomycin-loaded CS-ALG nanoparticles were negatively charged, with a size range of 380-420 nm, suitable for ocular application. The encapsulation efficiency was between 79 and 92 %, with decreasing alginate:daptomycin mass ratios. The antibacterial activity of daptomycin against major microorganisms responsible for bacterial endophthalmitis was not affected by encapsulation into nanoparticles. Daptomycin permeability was up to 16 % (chitosan nanoparticles) and 9 % (CS-ALG nanoparticles) through corneal cell monolayer, and 18 % (chitosan nanoparticles) and 12 % (CS-ALG nanoparticles) for retinal cell monolayer after 4 h, demonstrating epithelial retention of the drug compared to free drug. The developed daptomycin-loaded CS-ALG nanoparticles seem to be an interesting and potential system for ocular daptomycin delivery and treatment of bacterial endophthalmitis.

The antimicrobial activity of nanoparticles: present situation and prospects for the future

“…The key features of a drug delivery system are biodegradability, biocompatibility, controlled drug transport, and delivery to the target tissue. 83 …”

Polymeric nanoparticles – a novel solution for delivery of antimicrobial agents

“…Additionally, Hussein-Al-Ali et al reported strong antimicrobial potential of streptomycin-conjugated magnetic nanoparticles coated with chitosan against drug-sensitive S. aureus and its methicillin-resistant counterpart (MRSA), which might be a promising strategy to fight drug-resistant infections, particularity those reported in the hospital environment [46]. Recently, chitosancoated alginate (CS-ALG) nanoparticles were proposed for a facilitated ocular delivery system of daptomycin for the treatment of MRSA-originated endophthalmitis [49].…”

Recent Trends in Alginate, Chitosan and Alginate-Chitosan Antimicrobial Systems

“…A preliminary review of the literature showed the possibility of encapsulation into alginate-chitosan nanoparticles of various chemical structures of antimicrobial compounds like: benzoyl peroxide [76], gatifl oxacin [77], levofl oxacin [78], daptomycin [79], nisin [80] (Figure 7) and Ocimum sanctum methanolic extract [81].…”

“…Nanoparticles were prepared using ionotropic gelation (with or without some modifi cations) [76][77][78][79][80][81], freezedrying and spray-drying methods [82]. In the majority of cases, the nanoparticles obtained by ionotropic gelation method are stables (zeta potential -ζ < -30 mV or ζ > +30 mV) [77,80,81], have a nearly spherical shape, with sizes ranging from < 100 nm [76,78,81] to 200-900 nm [77,79,80].…”

“…In the majority of cases, the nanoparticles obtained by ionotropic gelation method are stables (zeta potential -ζ < -30 mV or ζ > +30 mV) [77,80,81], have a nearly spherical shape, with sizes ranging from < 100 nm [76,78,81] to 200-900 nm [77,79,80]. Freeze-drying and spray-drying methods allow obtaining of nanoparticles, together with microparticles, which have irregular shapes (fi brids-like) and sizes around 900 nm and larger, while spray-dried systems show higher antimicrobial activity than freeze-dried ones [82].…”