A Novel Strategy for Liposomal Drug Separation in Plasma by TiO(2) Microspheres and Application in Pharmacokinetics

PURPOSE: Liposomes are nano-scale materials with a biofilm-like structure. They have excellent biocompatibility and are increasingly useful in drug delivery systems. However, the in vivo fate of liposomal drugs is still unclear because existing bioanalytical methods for quantitation of total and liposomal-encapsulated drugs have limits. A novel strategy for liposomal-encapsulated drug separation from plasma was developed via the specific coordinate binding interaction of TiO(2) microspheres with the phosphate groups of liposomes. METHODS: Liposomal-encapsulated docetaxel was separated from plasma by TiO(2) microspheres and analyzed by the UPLC-MS/MS method. The amount of TiO(2), pH of the dilutions, plasma dilution factors and incubation time were optimized to improve extraction recovery. The characterization of the adsorption of liposome-encapsulated drugs by TiO(2) microspheres was observed by electron microscopy. For understanding the mechanism, pseudo-first and the pseudo-second order equations were proposed for the adsorption process. The study fully validated the method for quantitation of liposomal-encapsulated in plasma and the method was applied to the pharmacokinetic study of docetaxel liposomes. RESULTS: The encapsulated docetaxel had a concentration range of 15–4000 ng/mL from the plasma sample using a TiO(2) extraction method. Successful method validation proved the method was sensitive, selective and stable, and was suitable for quantitation of docetaxel liposomes in plasma samples. Extraction recovery of this method was higher than that of SPE method. As shown in electron microscopy, the liposomes adsorbed on TiO(2) microspheres were intact and there was no drug leakage. The study proposed pseudo-first and the pseudo-second order equations to facilitate the adsorption of liposomal drugs with TiO(2) microspheres. The proposed strategy supports the pharmacokinetic study of docetaxel liposomes in rats. CONCLUSION: TiO(2) extraction method was stable, reproducible, and reliable for quantitation of encapsulated docetaxel. Because of versatility of lipids, it is expected to a universal bioanalysis method for the pharmacokinetic study of liposomes.