OCULAR FORMULATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) IMPROVED ACTIVITY OF TEICOPLANIN AGAINST STAPHYLOCOCCUS AUREUS AND PSEUDOMONAS AERUGINOSA

Background and Aims. Teicoplanin (TEC) is regularly used for the topical treatment of severe ocular infections caused by Gram-positive bacteria. However, TEC is not used against Gram-negative bacteria because it cannot cross their outer membrane [1, 2]. Chronic and recalcitrant keratitis is associated with biofilm-producing resistant bacteria. Treatment for these diseases is limited because of bacterial resistance and the impossibility of using antibiotics formulated in a classical eyedrop for their high molecular weight. One promising approach in the field of antimicrobial therapy is the development of nano-drug delivery systems. Self-Nanoemulsifying Drug Delivery System (SNEDDS) loaded with teicoplanin (TEC), compared to free TEC, was evaluated to detect the most efficacy against resistant and/or biofilm forming strains of Staphylococcus aureus and Pseudomonas aeruginosa. Methods. TEC-loaded SNEDDS formulations were optimized by a Design of Experiment approach using the Response Surface Methodology [3]. TEC and TEC-loaded SNEDDS were tested against S. aureus and P. aeruginosa strains. Cytotoxicity by MTT assay on human corneal epithelial (HCE) cells, antibacterial susceptibility by microdilution techniques, and biofilm production by microtiter spectrophotometric method were assayed. Results and Conclusions. Reliable statistical model gave optimized SNEDDS for topical ocular application in terms of physico-chemical parameters. SNEDDS greatly increased the apparent solubility of TEC after reconstitution in aqueous environment. TEC-SNEDDS formulations at concentrations tested did not exert any cytotoxic effect. TEC-SNEDDS showed higher activity compared to free TEC, MIC values were reduced 2- fold against S. aureus (0.38 μg/mL) and methicillin-resistant S. aureus (MRSA) (0.09 μg/mL). Against biofilm, TEC-SNEDDS slightly reduced the biomass than free TEC. TEC and TEC-SNEDDS demonstrated no antibacterial activity against P. aeruginosa strains. However, TEC-SNEDDS at 0.047 μg/mL decreased the sessile cells of the biofilm-producing moderate strain, reducing biomass of 70%, while free TEC showed no antibiofilm effect. In conclusions, the results demonstrated that SNEDDS-TEC was more active than free TEC against S. aureus strains. Although TEC-SNEDDS did not demonstrate antibacterial activity on P. aeruginosa strains, it reduced biofilm biomass. Further studies are underway for new SNEDDS formulations by incorporating synergistic phytochemicals as adjuvants to enhance TEC activity.