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- Title
Quantitative evaluation of liposomal doxorubicin and its metabolites in spheroids.
- Authors
Lukowski, Jessica K.; Hummon, Amanda B.
- 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.
- Subjects
DOXORUBICIN; SMALL molecules; DRUG metabolism; METABOLITES; DRUG development; CELL culture; MASS spectrometry
- Publication
Analytical & Bioanalytical Chemistry, 2019, Vol 411, Issue 27, p7087
- ISSN
1618-2642
- Publication type
Article
- DOI
10.1007/s00216-019-02084-7