Design and Development of a New Type of Hybrid PLGA/Lipid Nanoparticle as an Ursolic Acid Delivery System against Pancreatic Ductal Adenocarcinoma Cells
Abstract
:1. Introduction
2. Results
2.1. Ursolic Acid Encapsulation Procedure and Characteristics of Obtained Nanoparticles
2.2. Stability Studies of UA-Loaded and Unloaded Nanoparticles
2.3. Hybrid UA-Loaded Nanoparticle Serum Stability Assay
2.4. Hybrid UA-Loaded Nanoparticle Characterization: Coating Dynamics and Encapsulation Efficiency Evaluation
2.5. Transmission Electron Microscopy (TEM) Visualization of Nanoparticles
2.6. Cellular Uptake of UA-S85-PLGA-PEG 2000 Nanoparticles
2.7. Assessment of UA-S85-PLGA-PEG 2000 Nanoparticles’ Toxicity toward Human Pancreatic Cancer Cell Lines
2.8. Hemolysis Assay
3. Discussion
4. Materials and Methods
4.1. Chemical and Reagents
4.2. Hybrid PLGA/Lipid Nanoparticle Preparation
4.3. Determination of Hybrid Nanoparticles’ Size and Zeta Potential
4.4. Determination of UA Encapsulation Efficiency (EE%)
4.5. Hybrid Nanoparticles’ Stability Evaluation
4.6. Analysis of Loaded and Unloaded UA-Hybrid Nanoparticles by Transmission Electron Microscopy
4.7. Cell Culture
4.8. MTT Cell Viability Assay
- AT = absorbance of the treatment well (treated cells);
- AC = absorbance of the control well (untreated cells).
4.9. Cellular Uptake
4.10. Determination of Hemolysis of Human Erythrocytes
4.11. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Sample Abbreviation | Sample Composition |
---|---|
UA-PLGA | Ursolic-acid-loaded PLGA nanoparticles |
UA-S100-PLGA | Ursolic-acid-loaded PLGA nanoparticles with lipid coats composed of pure SPC 90G |
UA-S95-PLGA-PEG 2000 | Ursolic-acid-loaded PLGA nanoparticles with lipid coats composed of SPC 90 and DSPE-PEG 2000 in molar ratio 95:5 |
UA-S85-PLGA-PEG 2000 | Ursolic-acid-loaded PLGA nanoparticles with lipid coats composed of SPC 90 and DSPE-PEG 2000 in molar ratio 85:15 |
Sample | PLGA | UA-PLGA | S100-PLGA | UA-S100-PLGA | S95-PLGA-PEG 2000 | UA-S95-PLGA-PEG 2000 | S85-PLGA-PEG 2000 | UA-S85-PLGA-PEG 2000 |
---|---|---|---|---|---|---|---|---|
Size [nm] | 110.6 ± 0.2 | 206.8 ± 3 | 167.2 ± 2.8 | 638.5 ± 445.7 | 146.3 ± 1 | 167.2 ± 2.7 | 130.3 ± 2.4 | 145.1 ± 2.6 |
PDI | 0.05 ± 0.01 | 0.26 ± 0.1 | 0.09 ± 0.01 | 0.63 ± 0.2 | 0.07 ± 0.01 | 0.08 ± 0.02 | 0.09± 0.02 | 0.1 ± 0.01 |
Zeta potential [mv] | −34.3 ± 1.1 | −30.4 ± 0.3 | −31.7 ± 0.7 | nd | −39.8 ± 0.9 | −32.5 ± 1 | −34.6 ± 3 | −42 ± 1.2 |
Sample | AsPC-1 | BxPC-3 | NHDF |
---|---|---|---|
UA-DMSO | 11.3 ± 1.7 | 17.9 ± 5.3 | 12.9 ± 3.9 |
UA-S85-PLGA-PEG 2000 | 8.6 ± 0.5 | 12.0 ± 5.7 | 15.4 ± 2.9 |
S85-PLGA-PEG 2000 | Non-toxic | Non-toxic | Non-toxic |
DMSO | Non-toxic | Non-toxic | Non-toxic |
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Markowski, A.; Jaromin, A.; Migdał, P.; Olczak, E.; Zygmunt, A.; Zaremba-Czogalla, M.; Pawlik, K.; Gubernator, J. Design and Development of a New Type of Hybrid PLGA/Lipid Nanoparticle as an Ursolic Acid Delivery System against Pancreatic Ductal Adenocarcinoma Cells. Int. J. Mol. Sci. 2022, 23, 5536. https://doi.org/10.3390/ijms23105536
Markowski A, Jaromin A, Migdał P, Olczak E, Zygmunt A, Zaremba-Czogalla M, Pawlik K, Gubernator J. Design and Development of a New Type of Hybrid PLGA/Lipid Nanoparticle as an Ursolic Acid Delivery System against Pancreatic Ductal Adenocarcinoma Cells. International Journal of Molecular Sciences. 2022; 23(10):5536. https://doi.org/10.3390/ijms23105536
Chicago/Turabian StyleMarkowski, Adam, Anna Jaromin, Paweł Migdał, Ewa Olczak, Adrianna Zygmunt, Magdalena Zaremba-Czogalla, Krzysztof Pawlik, and Jerzy Gubernator. 2022. "Design and Development of a New Type of Hybrid PLGA/Lipid Nanoparticle as an Ursolic Acid Delivery System against Pancreatic Ductal Adenocarcinoma Cells" International Journal of Molecular Sciences 23, no. 10: 5536. https://doi.org/10.3390/ijms23105536