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K. Jyothi*, A. Anil Kumar and Srinivasa Rao


Gemcitabine is a potent anticancer drug approved for the treatment of pancreatic, non-small-cell lung, breast, and ovarian cancers. Gemcitabine is a highly reactive molecule and binds extensively to plasma and tissue proteins leading to a fast inactivation of a large part of the administered dose. Thus, the clinical use of Gemcitabine faces two major problems, serious dose-limiting toxicities and rapid inactivation of the drug in the circulation. Both problems could possibly be prevented by shielding of the drug from the extracellular environment by means of a lipid coating. In the present investigation Gemcitabine loaded long circulating liposomes were prepared by thin film hydration method. By using different concentrations of PEGylated phospholipids, from the preliminary in vivo work, it was observed that stealth liposome’s formulation was better than free Gemcitabine. Stealth liposome’s formulation decreased the volume of solid tumor as well as ascites volume, decreased average body weight and increased the life span. In vivo pharmacokinetic studies were carried out in lymphoma bearing mice and the drug was detected in plasma even after 24 hours. This reveals that the stealth liposome’s formulation had improved stability in the biological fluids. Tissue distribution studies done in the drug loaded long circulating liposome’s showed preferential drug targeting to liver followed by spleen, lungs, and kidneys. Higher concentration of drug was targeted to the organs after administering the dose in the form of long circulating liposomes except in the heart. Drug levels in the heart are closely related to the inherent cardiac toxicity of Gemcitabine. Therefore using liposomal Gemcitabine formulation could reduce the cardiac toxicity of Gemcitabine.

Keywords: Gemcitabine, Liposomes, PEGylated phospholipids, Cancer.

[Full Text Article]

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