An Ex Vivo Evaluation of Moxifloxacin Nanostructured Lipid Carrier Enriched In Situ Gel for Transcorneal Permeation on Goat Cornea

J Pharm Sci. 2019 Sep;108(9):2905-2916. doi: 10.1016/j.xphs.2019.04.005. Epub 2019 Apr 9.

Abstract

The study was designed to fabricate the moxifloxacin nanostructured lipid carriers (MOX-NLCs) loaded in situ gel for opthalmic application to improve the corneal permeation and retention and also subside the toxic effect associated with intracameral injection of moxifloxacin in endophthalmitis treatment. Initially, Box-Behnken design was used to optimize the various factors significantly affecting the final formulation attributes. MOX-NLCs with particle size 232.1 ± 9.2 nm, polydispersity index 0.247 ± 0.031, zeta potential -16.3 ± 1.6 mV, entrapment efficiency 63.1 ± 2.4%, and spherical shape was achieved. The optimized MOX-NLCs demonstrated the Higuchi release kinetics with highest regression coefficient. Besides this, FTIR, differential scanning calorimetry, and X-ray diffraction results suggested that MOX had excellent compatibility with excipients. Furthermore, the results of ex-vivo permeation study demonstrated 2-fold higher permeation (208.7 ± 17.6 μg), retention (37.26 ± 2.83 μg), and flux (9.57 ± 0.73 μg/cm2 h) compared with free MOX in situ gel. In addition, MOX-NLCs exhibited normal corneal hydration and did not show any sign of structural damage to the corneal tissue as confirmed by histology. Therefore, the findings strongly suggest that MOX-NLCs in situ gel with higher permeation and retention can be a better alternative strategy to prevent and treat the endophthalmitis infection.

Keywords: drug delivery system(s); factorial design; lipid nanoparticle(s) (LNP); nanoparticle(s); ophthalmic drug delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Ophthalmic
  • Alginates / chemistry
  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacokinetics*
  • Calorimetry, Differential Scanning
  • Cornea / metabolism*
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Drug Stability
  • Endophthalmitis / drug therapy
  • Endophthalmitis / microbiology
  • Gels
  • Goats
  • Humans
  • Hypromellose Derivatives / chemistry
  • Lipids / chemistry*
  • Microbial Sensitivity Tests
  • Moxifloxacin / administration & dosage
  • Moxifloxacin / pharmacokinetics*
  • Nanoparticles / chemistry
  • Permeability
  • Staphylococcus aureus / drug effects
  • X-Ray Diffraction

Substances

  • Alginates
  • Anti-Bacterial Agents
  • Drug Carriers
  • Gels
  • Lipids
  • Hypromellose Derivatives
  • Moxifloxacin