Objectives: To investigate and evaluate the transdermal delivery of ethosomes bearing vancomycin hydrochloride, a glycopeptide antibiotic with a relatively high molecular weight (1485.7Da).Methods: Vancomycin loaded ethosomes were prepared by cold method technique and characterized for vesicular shape, vesicular size, entrapment efficiency, zeta potential, in vitro drug permeation, microbiological assay against methicillin resistant Staphylococcusaureus (MRSA) and stability.Results: Microscopic examinations suggested ethosomes as unilamellar spherical vesicles. Vesicle size, entrapment efficiency and zeta potential values were depending on concentration of membrane components. Ethosomal formula having 1% phospholipid, 45% ethanol and 10% propylene glycol (F13) showed the smallest mean particle size (71.60nm±17.6) and highest transdermal flux (414.7 µg/cm2. hr) across hairless rat skin which was 72.67 times drug solution. The results obtained from microbiological assay suggested that the minimum inhibitory concentration (MIC) is affected by surface charge of ethosomes. The optimized formula on storage at 4°C for 90 days retained 89.82%±1.00 of initial drug content.Conclusions: The results collectively suggest that ethosomes are efficient carrier for transdermal delivery of vancomycin hydrochloride
