Towards the Development of Long Circulating Phosphatidylserine (PS)- and Phosphatidylglycerol (PG)-Enriched Anti-Inflammatory Liposomes: Is PEGylation Effective?
Abstract
:1. Introduction
- Are the biodistribution profiles of PS- and PG-enriched nanodispersions in healthy mice comparable?
- Does PEGylation of PS- and PG-enriched nanodispersions effect their biodistribution in healthy mice?
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Liposome Preparation
2.2.2. Dynamic Light Scattering (DLS)
2.2.3. Cryo-Transmission Electron Microscopy (Cryo-TEM)
2.2.4. Zeta Potential Measurements
2.2.5. Mice
2.2.6. Experimental Design for the Evaluation of In Vivo and Ex Vivo Biodistribution
2.2.7. Fluorescence Imaging (FI)
2.2.8. Statistical Analysis
3. Results
3.1. Physico-Chemical Characterization Showed Defined Size and Charge of DiR-Loaded Liposomes
3.2. In Vivo Liposome Biodistribution Differed in Biodistribution and Abdominal Accumulation, Depending on Both Formulation and PEGylation
3.3. Quantification of In Vivo Fluorescence Signal Showed Prolonged Circulation of S100PEG and Fast Clearance of Other Formulations
3.4. Quantification of Ex Vivo Single Organ TREs Shows Systemic Accumulation of S100 PEG and Fast Clearance of Other Formulations via Liver and Spleen
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Liposomal Formulation | Z-Average (nm) | PDI | Zeta Potential (mV) in Saline | Zeta Potential (mV) in Glucose 5% |
---|---|---|---|---|
S100 | 125 ± 6 | 0.06 ± 0.01 | −0.9 ± 1.4 | 0.3 ± 0.3 |
S100 PEG | 116 ± 13 | 0.06 ± 0.01 | −2.5 ± 1.5 | −9.1 ± 0.8 |
PS | 125 ± 11 | 0.07 ± 0.01 | −26.9 ± 1.3 | −60.0 ± 3.9 |
PS PEG | 115 ± 10 | 0.06 ± 0.01 | −4.2 ± 2.0 | −16.0 ± 1.4 |
PG | 120 ± 4 | 0.08 ± 0.02 | −27.1 ± 2.1 | −57.8 ± 1.5 |
PG PEG | 116 ± 13 | 0.06 ± 0.01 | −3.7 ± 1.2 | −16.1 ± 2.6 |
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Klein, M.E.; Rieckmann, M.; Sedding, D.; Hause, G.; Meister, A.; Mäder, K.; Lucas, H. Towards the Development of Long Circulating Phosphatidylserine (PS)- and Phosphatidylglycerol (PG)-Enriched Anti-Inflammatory Liposomes: Is PEGylation Effective? Pharmaceutics 2021, 13, 282. https://doi.org/10.3390/pharmaceutics13020282
Klein ME, Rieckmann M, Sedding D, Hause G, Meister A, Mäder K, Lucas H. Towards the Development of Long Circulating Phosphatidylserine (PS)- and Phosphatidylglycerol (PG)-Enriched Anti-Inflammatory Liposomes: Is PEGylation Effective? Pharmaceutics. 2021; 13(2):282. https://doi.org/10.3390/pharmaceutics13020282
Chicago/Turabian StyleKlein, Miriam E., Max Rieckmann, Daniel Sedding, Gerd Hause, Annette Meister, Karsten Mäder, and Henrike Lucas. 2021. "Towards the Development of Long Circulating Phosphatidylserine (PS)- and Phosphatidylglycerol (PG)-Enriched Anti-Inflammatory Liposomes: Is PEGylation Effective?" Pharmaceutics 13, no. 2: 282. https://doi.org/10.3390/pharmaceutics13020282