Quantitative evaluation of liposomal doxorubicin and its metabolites in spheroids.

Quantitative evaluation of liposomal doxorubicin and its metabolites in spheroids.
Anal Bioanal Chem. 2019 Aug 30;:
Authors: Lukowski JK, Hummon AB
Abstract
Accurate measurement and understanding of therapeutic uptake and metabolism is key in the drug development process. This work examines the amount of doxorubicin that can penetrate into spheroids after being encapsulated in a liposomal configuration in comparison with free drug. Through a process known as serial trypsinization, three distinct cellular populations of a spheroid were successfully separated and a small molecule extraction was used to isolate the chemotherapeutic. Doxorubicin showed a time-dependent permeability into spheroids with the most drug accumulating in the core at 24 h of treatment. Entrapment of the chemotherapeutic delayed the permeability of the drug and resulted in reduced amounts quantified at the earlier time points. These findings validate the claim that liposomal therapeutics have the ability to alter the pharmacokinetics and pharmacodynamics profiles of a drug while also demonstrating the combined power of mass spectrometry and three-dimensional cell cultures to evaluate drug penetration and metabolism. Graphical abstract.
PMID: 31471684 [PubMed - as supplied by publisher]

Source: Analytical and Bioanalytical Chemistry - August 29, 2019 Category: Chemistry Authors: Lukowski JK, Hummon AB Tags: Anal Bioanal Chem Source Type: research