Preparation of ketoconazole liposomes with an ultrasonic and an injection method using vegetable oils

Abstract

Introduction: Ketoconazole as antimycotic drug have a great impact in the treatment of many skin diseases. The toxicity of available ketoconazole in form of tablets, cream and shampoo is overcome by encapsulation in liposome structures which show potential benefits in aspect of biodegradability, increased stability and prolonged drug releasing. Objectives: The main objective of this study was to develop new formulations of ketoconazole liposomes characterized with satisfactory encapsulation efficiency and stability. Methods: Liposomes were prepared by an ultrasound and an injection method. In the liposome preparation, sunflower and olive were introduced instead of harmful organic solvents. The obtained liposomes were characterized according to the encapsulation efficiency, zeta potential, electrical conductivity, morphological appearance, particle size and stability. The highest encapsulation efficiency of 70.33% and 87.06% was obtained using ketoconazole:cholesterol:L-α-phosphatidylcholine in the ratio of 1:2:1.67 w/w/w and 3.33:1:3.33 w/w/w, respectively, at the ultrasound and the injection method, using water at hydration medium, oil as solvent and centrifugation at 5000 rpm. During one month storage, the stability of obtained liposomes was higher at 4ºC compared to 25ºC. By application of the ultrasound method small unilamellar ketoconazole liposomes were formed, while large unilamellar and multilamellar by injection method. Conclusion: Introducing the sunflower and the olive oil, eco friendly preparation method was established, as well as new formulations of ketoconazole liposomes were developed.