Preclinical development of MGO Manuka Honey microemulsion for blepharitis management

OBJECTIVE: To evaluate the in vitro antimicrobial effects of cyclodextrin-complexed and uncomplexed Manuka honey on bacteria commonly associated with blepharitis, and in vivo rabbit eye tolerability of a cyclodextrin-complexed methylglyoxal (MGO) Manuka Honey microemulsion (MHME). METHODS AND ANALYSIS: In vitro phase: Bacterial growth inhibition was assessed by area under the growth curve (AUC) for Staphylococcus aureus, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for S. aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa with cyclodextrin-complexed and uncomplexed Manuka honey were determined. In vivo phase: Six rabbits were administered 20 µL of MHME (at 1:10 dilution) to the right eye (treated) and 20 µL of saline to the left eye (control) daily, for 5 days. Tear evaporation, production, osmolarity, lipid layer, conjunctival hyperaemia and fluorescein staining were assessed daily, before and 15 min after instillation. RESULTS: In vitro phase: The relative AUC for cyclodextrin-complexed Manuka honey was lower than that of uncomplexed honey at both 250 and 550 mg/kg of MGO (both p <0.05). Cyclodextrin-complexed honey had lower MIC and MBC than uncomplexed honey for both S. aureus and S. epidermidis, but not P. aeruginosa. In vivo phase: No significant changes were observed in the parameters assessed in either treated or control eyes (all p >0.05). CONCLUSION: Overall, antimicrobial potency of cyclodextrin-complexed Manuka honey was greater than uncomplexed honey. No significant immediate or cumulative adverse effects were observed with MHME application on rabbit eyes, supporting future conduct of clinical safety and tolerability trials in human subjects.