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Development, Optimization, and In Vitro/In Vivo Characterization of Enhanced Lipid Nanoparticles for Ocular Delivery of Ofloxacin: the Influence of Pegylation and Chitosan Coating

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Abstract

This study aims to investigate whether modification of solid lipid nanoparticles (SLNs) with chitosan (CTS) and polyethylene glycol (PEG) coatings enhances corneal retention time and transcorneal bioavailability. Ofloxacin (OFLOX) was selected as the model drug because of its potential benefits for the treatment of local eye infections. The OFLOX-CTS-PEG-SLN was prepared by a modified emulsion/solvent evaporation technique. A central composite design was implemented to investigate the influence of total lipid/drug ratio, surfactant concentration, PEG stearate concentration in the lipid mixture, and CTS concentration on size, entrapment, transcorneal permeation, and adhesion to the corneal mucosal membrane. The optimized OFLOX-CTS-PEG-SLN was characterized for OFLOX cumulative percentage released in simulated tear fluid and permeated across the excised bovine corneal membrane. Moreover, nanoparticle morphology, eye irritation via histopathological analysis, and OFLOX concentration in the ocular fluids and tissues were determined. A total lipid/drug ratio of 19:1, Tween 80 of 2%, PEG stearate concentration in the lipid mixture (% w/w) of 2.6%, and CTS concentration (% w/v) of 0.23% produced 132.9 nm particles entrapping 74.8% of the total drug added. The particles detached from the corneal membrane at a force of 3700 dyne/cm2. The %OFLOX released from the optimized nanoparticles was 63.3, and 66% of the drug permeated after 24 h. Compared to Oflox® drops, the optimized OFLOX-CTS-PEG-SLN exhibited similar tolerability but two- to threefold higher concentrations in the eyes of rabbits. Coating of SLN with chitosan and PEG augments the ocular bioavailability of OFLOX by increasing transcorneal permeation and enhancing mucoadhesion strength.

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Correspondence to Mohammed H. Elkomy.

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Eid, H.M., Elkomy, M.H., El Menshawe, S.F. et al. Development, Optimization, and In Vitro/In Vivo Characterization of Enhanced Lipid Nanoparticles for Ocular Delivery of Ofloxacin: the Influence of Pegylation and Chitosan Coating. AAPS PharmSciTech 20, 183 (2019). https://doi.org/10.1208/s12249-019-1371-6

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KEY WORDS

  • ocular bioavailability
  • ofloxacin
  • lipid nanocarriers
  • chitosan
  • polyethylene glycol stearate
  • transcorneal permeation
  • bioadhesion