Novel nanostructured lipid carrier-based inserts for controlled ocular drug delivery: evaluation of corneal bioavailability and treatment efficacy in bacterial keratitis

Abstract

Objectives: The aim of the present study was to develop novel ofloxacin (OFX)-loaded nanostructured lipid carrier (NLC)-based inserts for ocular application for treatment of bacterial keratitis.

Methods: NLC loaded with 0.3% OFX was prepared by means of high shear homogenization and 0.75% chitosan oligosaccharide lactate (COL) was added. Glycerin or PEG 400 at the range of 1 – 15% was added to NLCs as plasticizers and inserts were developed by solvent casting evaporation. Characterization, in vitro release, microbiological, ex vivo and in vivo studies were performed.

Results: The inserts developed with the addition of glycerin (Ins3_OFX) was found as optimal. The kinetic studies revealed that the release of Ins3_OFX was a combination of diffusion and swelling. Ins3_OFX was more bioadhesive in texture profile analysis studies. In the in vivo studies performed with rabbits, the pre-ocular retention time was enhanced up to 24 h and C_max was increased almost six times in comparison with commercial. The rabbits were infected with Staphylococcus aureus and keratitis was confirmed. This group was treated with Ins3_OFX and they recovered in 7 days with no significant sign of conjunctival redness and corneal opacity.

Conclusion: NLC-based inserts developed with COL and glycerin may be offered as appropriate vehicles for ocular delivery.

Keywords:

• chitosan oligosaccharide lactate
• insert
• nanoparticle
• nanostructured lipid carrier
• ocular
• ofloxacin

Acknowledgments

The authors would like to thank Ege University, Faculty of Pharmacy, Department of Microbiology and Pharmaceutical Sciences Research Center (FABAL) for U-HPLC studies and DSC facilities.

Declaration of interest

This study was supported by Ege University, Scientific Research Projects No: 10/ECZ/014. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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