Abstract
In this research the selective delivery of drug by liposomes to solid tumors as compared to healthy tissues is studied. Liposomes are small spheres (typically about 30-500 nm in diameter and preferably about 200 nm or less) in which drugs can be encapsulated. As long as the drug is encapsulated it cannot cause toxic and therapeutic effects. The drug has to be released from the liposomes to do so. Therefore, knowledge of the individual encapsulated and released drug concentrations is essential to understand and improve drug delivery by liposomes. While such individual concentrations in plasma have been reported, these are rarely measured in tumor and healthy tissues due to practical complications.
In this study, such individual concentrations in murine blood and tissues were measured by using liposomes containing prednisolone phosphate as a model formulation. The rapid conversion of prednisolone phosphate into prednisolone after release of prednisolone phosphate from the liposomes enables the separate quantification of encapsulated and released drug, respectively. The corresponding analytical methodology was appropriately developed and validated to obtain reliable results. Implementation of the methodology shows that, from a quantitative point of view, the availability of released drug in the tumor is not pronounced as compared to the liver, spleen and kidneys. However, extended drug release is observed in the tumor and probably contributes to the beneficial effect. The probably rapid redistribution of prednisolone from the tissues after drug release from the liposomes highlights the impact of the properties of the drug compound itself on the liposomal drug delivery effect. It is therefore suggested that, from a pharmacodynamic point of view, further research should focus on released drug concentrations instead of the drug release.
Original language | English |
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Qualification | Doctor of Philosophy |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 19 Jun 2019 |
Publisher | |
Print ISBNs | 978-94-6361-280-7 |
Publication status | Published - 19 Jun 2019 |
Keywords
- bioanalysis
- dephosphorylation
- drug availability
- in vivo drug release
- liposomes
- modeling
- pharmacokinetics
- prednisolone phosphate
- separate quantification
- tumor targeted drug delivery