Liposomal Encapsulation of Amikacin Sulphate for Optimizing Its Efficacy and Safety

Abstract

Aims: The abstract of the current study was to formulate amikacin sulfate in a liposomal formulatiom for enhancing its efficacy and safety. Place and Duration of Study: Pharmaceutical Technology Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Dokki, Cairo, Egypt, between 2010-2013. Methodology: Amikacin sulfate liposomes were prepared by the vortex dispersion method using dipalmitoyl phosphatidyl choline (DPPC), cholesterol (CHOL) and charge inducing agent (CIA). Dicetyl phosphate (DCP) and Stearyl amine (SA) were added as the negative and positive charge inducing agents respectively. Characterization of the prepared amikacin sulphate liposomes was performed. In-vitro release of selected formulations was estimated. A stability study for 45 days was performed. Investigation of the optimum dose for sterilization of amikacin sulfate liposomes was carried out. Selected amikacin sulfate liposomal formulations activities were evaluated against Escherichia coli infection in mice and compared to the free drug. Results: The entrapment efficiencies ranged from 43.6±1.81 to 62.5±2.57%, the vesicles are well identified and present in a nearly perfect sphere like shape ranging in size from 54.3±11 to 362.1±56 nm and the polydospersity index values of all liposomal formulations were < 0.3. DSC of different liposomal formulations shows a change in transition temperature of the main phospholipids. In-vitro release profiles revealed biphasic release of the drug from liposomes. Physical stability performed at 2-8oC for 45 days revealed low leakage of drug from all liposomal formulations investigated. Sterilization using gamma radiations revealed that a dose of 25 KGy was the optimum sterilization dose. The results also revealed less number of colonies forming units (cfu/ml) in the case of amikacin sulfate liposomes than the unentrapped drug. Conclusion: It can be fulfilled from this work that amikacin sulfate liposomes represent promising carrier for delivery of amikacin offering good physical stability, high entrapment effeciencies and controlled drug release.