Docetaxel in liposomes: the effect of lipid composition on the achieved drug entrapment

Abstract

INTRODUCTION: Docetaxel (DOC) is a potent anticancer drug but has several limitations such as poor solubility. The currently commercially available formulation of DOC is limited by reported serious side effects which either is attributed to the drug itself or the solvent used. Nanomedicine has been used for improving the therapeutic outcome of several drugs, but so far there are none available with DOC. It would be interesting to apply a liposomal formulation for delivery of DOC in order to solubilize the drug and improve the therapeutic outcome. OBJECTIVES: The aim with this master project was to establish a small-scale screening method for making and characterizing DOC liposomes and further investigate the effect of lipid composition on drug entrapment to find a suitable liposomal formulation of DOC. METHODS: DOC liposomes were made of different lipid compositions by a thin-film hydration method and size reduced by probe sonication. Centrifugation was used to remove free DOC from the liposomal formulation. The effect on varying lipid compositions on drug entrapment were tested with characterization of the liposomal formulations. RESULTS: The 14 different liposomal formulations with varying lipid compositions and a drug:lipid ratio of 1:10 (w/w) showed an entrapment efficiency between 18 and 115 %. Three of the liposomal formulations showed entrapment efficiency near 100 % and were further investigated by increasing the drug:lipid ratio to 2:10 (w/w) to see if more DOC could be entrapped in the liposomes. The DOC recovery were low for all three formulations, although the soy phosphatidylcholine (SPC):DOTAP liposomes showed a higher recovery compared to the other two. The SPC:DOTAP were brought further to investigate the effect of varying the concentration of DOTAP, and the results showed that a higher DOTAP concentration gave a higher recovery of DOC. CONCLUSION: A small scale screening method for investigating the effect of different liposomal formulations on the archived DOC entrapment was established successfully. The liposomes with cationic lipid, DOTAP, showed best entrapment efficiency of the different liposomal combinations screened. Increasing amount of DOTAP within SPC:DOTAP liposomes showed a greater incorporation of DOC. Key words: docetaxel, liposomes, lipids, lipid composition, drug carrier, formulation, entrapment efficiency.