Cefazolin-loaded Solid Lipid Microparticles: A novel approach for ocular therapeutics

Introduction

Eye infections present major challenges for treatment, due to the microbial species and the low ocular bioavailability of drug. A fortified eye drop is, in some case, the only option for administering antibiotics such as Cefazolin. It is an extemporaneous preparation with limit stability and needs to be injected via the painful intraocular route. In order to improve ocular tolerance and the efficacy of Cefazolin, we developed a colloidal eye drop containing lipid microparticles loaded with this drug which can be administrable by instillation.

Methods

Cefazolin lipid microparticles were prepared by high shear homogenization method using an Ultraturrax at 20,000 rpm for 5 minutes. The lipid matrix was composed of carnauba wax and a pair of surfactants. The particle size was evaluated by optical microscopy, while encapsulation efficiency was performed by spectrophotometry at 272nm in water. The in vitro release study was conducted in dialysis bag immersed in artificial tear fluid. Microbiological efficacy was assessed on sensitive strains of Pseudomonas aeruginosa and Escherichia coli. Ocular tolerability was assessed by a HET CAM test on embryonated test.

Results

The lipid microparticles exhibited a monodisperse distribution with a mean diameter of 1.1 µm. The recorded encapsulation efficiency was 87% and the antimicrobial activity was satisfactory. The in vitro release of the colloidal eye drop demonstrated enhanced diffusion and a delayed release profile, with a Cmax shift of 50 minutes compared to the aqueous solution of cefazolin. The pH and osmolarity were favorable for ocular administration. The HETCAM results didn’t show any sign of irritation at 5 min.

Conclusion

The colloidal eye drop of lipid microparticles encapsulating Cefazolin represents a promising advance in the treatment of eye infections, aiming to enhance intraocular permeability and prolong the action of the antibiotic.