Secretory phospholipase A₂ responsive liposomes
Guodong Zhu1, Jason N Mock1, Ibrahim Aljuffali2
1Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602.
Journal of Pharmaceutical Sciences
|April 2, 2011
Summary
Secretory phospholipase A(2) (sPLA(2)) affects liposome drug release. DSPE-PEG enhanced sPLA(2)-mediated release, offering insights for cancer and inflammation treatments.
Area of Science:
- Biochemistry
- Materials Science
- Pharmacology
Background:
- Secretory phospholipase A(2) (sPLA(2)) expression is elevated in various cancers.
- sPLA(2) can trigger the release of substances from lipid carriers.
- Understanding sPLA(2) interactions with drug delivery systems is crucial.
Purpose of the Study:
- To investigate the impact of secretory phospholipase A(2) (sPLA(2)) on diverse liposome formulations.
- To determine the influence of specific phospholipid compositions on sPLA(2)-mediated release.
- To evaluate the utility of ESI-MS and 6-CF release assays for assessing liposomal stability.
Main Methods:
- Utilized electrospray ionization mass spectrometry (ESI-MS) to analyze liposome composition.
- Employed 6-carboxyfluorescein (6-CF) release assays to quantify payload leakage.
- Examined various zwitterionic and anionic phospholipid combinations, including DSPE and DSPE-PEG, with and without cholesterol.
Main Results:
- 1,2-distearoyl-sn-glycero-3-phosphatidylglycerol (DSPG) and DSPE were most susceptible to sPLA(2) degradation.
- Incorporation of 10 mol% DSPE and anionic lipids increased 6-CF release.
- DSPE-PEG enhanced sPLA(2)-mediated release, while cholesterol reduced it. Group IIa sPLA(2) activity was less than Group III.
Conclusions:
- ESI-MS and 6-CF release are effective tools for evaluating sPLA(2) selectivity and liposome release kinetics.
- Different sPLA(2) isoforms exhibit varying activities.
- Lipid selection, particularly DSPE-PEG, can optimize sPLA(2)-mediated drug release for inflammatory diseases and cancers.
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