Pharmacokinetic and Pharmacodynamic Evaluation of Gemifloxacin Chitosan Nanoparticles As an Antibacterial Ocular Dosage Form.

ABSTRACT

Ocular infections are classified into superficial keratitis, conjunctivitis or deep infections such as corneal abscesses and blepharitis. Herein, we focused on the development of formulation approaches that could prolong the residence time of gemifloxacin (GM) and enhance its corneal penetration to facilitate GM effects both superficially and at the deep tissues. Ionic gelation method was used to prepare eight forms of GM nanoparticles (NPs) formulated from chitosan polymer using sodium tripolyphosphate (TPP)-induced precipitation method. Differential scanning colorimetry (DSC) and X-ray diffraction (XRD) demonstrated the interaction between the chitosan and GM. Particle size, entrapment efficiency and cumulative in vitro release were used to select the optimal formula using Design Expert® software. The mean diameter of the selected NPs was 158. 4 nm. The average entrapment efficiency and cumulative release exhibited by the formulated NPs were 46.6% and 74.9%, respectively. Pharmacokinetics studies carried out on rabbits revealed that the ocularly-administered NPs significantly increased the loaded GM concentration in the tear and aqueous humour samples that suggested enhancement of precorneal retention and transcorneal permeation, respectively. Furthermore, ocular pharmacodynamic studies conducted on rabbits following ocular infection with Staphylococcus aureus or Pseudomonas aeruginosa showed that the administered NPs augmented the antibacterial activity of the delivered GM. This was demonstrated via the histopathological examination of the dissected corneas that showed preserved histological features and reduced bacterial keratitis on using the GM NPs rather than GM solution. Moreover, the GM NPs-treated corneas showed lower viable bacterial counts than the GM solution-treated corneas. Accordingly, our study illustrated the capability of the chitosan NPs to promote the antibacterial activity of GM against eye infections via ocular administration.