A rapid and efficient technique for liposomal and nonliposomal drug pharmacokinetics studies using magnetic nanoprobes and its application to leakage kinetics of liposomes

Abstract

Currently, the pharmacokinetics of liposomes was researched in vivo by measuring the total amount of drug in plasma. This method of using the total drug amount instead of the free drug amount virtually increase the apparent exposure and apparent biological distribution. To solve this problem, we developed a rapid and efficient method by using well-established streptavidin-functional Fe3O4@PDA as the separation nanoprobes to efficiently isolate biotin-labeled DTX-liposomes over 75% from plasma in the presence of magnetic field. The isolation procedure takes only 20 min and the concentration of DTX in liposomes from plasma was determined by LC–MS/MS. The method for the determination of DTX in plasma was linear in the range of 5–5000 ng/mL, and the correlation coefficient was 0.9989. Results obtained in this study clearly demonstrated that the pharmacokinetic parameters of non-liposomal drug and total drug are different in vivo. Therefore, traditional method for studying the pharmacokinetics of liposomes in vivo is unreasonable, and the new method mentioned here provided a strategy for studying the pharmacokinetics of liposomes.