Design of Besifloxacin HCl-Loaded Nanostructured Lipid Carriers: In Vitro and Ex Vivo Evaluation.

Objective

In the treatment of severe cases of bacterial keratitis, conventional eye drops containing antibiotics should be applied daily and very frequently. The aim of this study is to develop low-dose high-effect formulations with the prepared nanostructured lipid carrier (NLC) formulations to reduce antibiotic resistance and increase patient compliance.

Methods

NLC formulations were loaded with besifloxacin HCl (BHL) and the besifloxacin HCl: sulfobutyl ether beta-cyclodextrin (SBE-CD) complex. Positive charge was gained with chitosan, and corneal permeation and resolubility were increased with SBE-CD. In vitro characterization studies, permeability studies, and cytotoxicity and ex vivo transport studies were carried out.

Results

In this study, it was found that SBE-CD increased BHL's solubility by 8-fold based on phase solubility studies. The optimized NLCs were small in size (13.63-16.09 nm) with a low polydispersity index (0.107-0.181) and adequate BHL drug loading efficiency. In vitro release studies showed that formulations were released approximately for 8 h and at levels over the minimum inhibitory concentration of Pseudomonas aeruginosa and Staphylococcus aureus. NLC formulations had a better corneal permeation rate than the marketed product during 6 h of ex vivo studies.

Conclusions

According to in vitro and ex vivo data, it was determined that the most favorable NLC formulation was the formulation containing BHL/SBE-CD that was covered with chitosan. It has the highest drug loading capacity and one of the highest ex vivo corneal passage levels, along with desired drug release. The formulation containing BHL/SBE-CD and chitosan can be a potential alternative for the treatment of bacterial keratitis.