PUBLICATION
Two Types of Liposomal Formulations Improve the Therapeutic Ratio of Prednisolone Phosphate in a Zebrafish Model for Inflammation
- Authors
- Xie, Y., Papadopoulou, P., de Wit, B., d'Engelbronner, J.C., van Hage, P., Kros, A., Schaaf, M.J.M.
- ID
- ZDB-PUB-220226-2
- Date
- 2022
- Source
- Cells 11(4): (Journal)
- Registered Authors
- Schaaf, Marcel J. M., Xie, Yufei
- Keywords
- glucocorticoids, inflammation, laser wounding, liposome, zebrafish
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/pharmacology
- Anti-Inflammatory Agents/therapeutic use
- Glucocorticoids/pharmacology
- Glucocorticoids/therapeutic use
- Inflammation/drug therapy
- Liposomes*
- Polyethylene Glycols
- Prednisolone/analogs & derivatives
- Tissue Distribution
- Zebrafish*
- PubMed
- 35203318 Full text @ Cells
Citation
Xie, Y., Papadopoulou, P., de Wit, B., d'Engelbronner, J.C., van Hage, P., Kros, A., Schaaf, M.J.M. (2022) Two Types of Liposomal Formulations Improve the Therapeutic Ratio of Prednisolone Phosphate in a Zebrafish Model for Inflammation. Cells. 11(4):.
Abstract
Glucocorticoids (GCs) are effective anti-inflammatory drugs, but their clinical use is limited by their side effects. Using liposomes to target GCs to inflammatory sites is a promising approach to improve their therapeutic ratio. We used zebrafish embryos to visualize the biodistribution of liposomes and to determine the anti-inflammatory and adverse effects of the GC prednisolone phosphate (PLP) encapsulated in these liposomes. Our results showed that PEGylated liposomes remained in circulation for long periods of time, whereas a novel type of liposomes (which we named AmbiMACs) selectively targeted macrophages. Upon laser wounding of the tail, both types of liposomes were shown to accumulate near the wounding site. Encapsulation of PLP in the PEGylated liposomes and AmbiMACs increased its potency to inhibit the inflammatory response. However, encapsulation of PLP in either type of liposome reduced its inhibitory effect on tissue regeneration, and encapsulation in PEGylated liposomes attenuated the activation of glucocorticoid-responsive gene expression throughout the body. Thus, by exploiting the unique possibilities of the zebrafish animal model to study the biodistribution as well as the anti-inflammatory and adverse effects of liposomal formulations of PLP, we showed that PEGylated liposomes and AmbiMACs increase the therapeutic ratio of this GC drug.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping