Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cell Lines and Culture
2.3. Preparation of Met Loaded Liposomes
2.4. Physicochemical Characterization of Liposomes
2.4.1. Particle Size and Polydispersity Index (PDI)
2.4.2. Cryo Transmission electron microscopy (TEM)
2.4.3. UPLC Method of Analysis
2.4.4. Entrapment Efficiency and % Drug Loading
2.4.5. In Vitro Drug Release
2.5. Differential Scanning Calorimetry (DSC) Studies
2.6. Powder X-ray Diffraction (PXRD) Studies
2.7. Stability Studies
2.8. In Vitro Cellular Uptake Studies
2.9. In Vitro Cytotoxicity Assay
2.10. Cell Migration Assay
2.11. Clonogenic Assay
2.12. Caspase Enzymatic Activity Assay—Apoptosis-Induced Cell Death
2.13. Western Blot Analysis
2.14. In Vitro Tumor Simulation Studies
2.15. Statistical Analysis
3. Results
3.1. Formulation Fabrication, Optimization, and Characterization
3.2. In Vitro Drug Release
3.3. Thermal Analysis (DSC Studies)
3.4. Powder X-ray Diffraction (PXRD) Studies
3.5. Stability Studies
3.6. Cellular Uptake Studies
3.7. Cytotoxicity Studies
3.8. Cell Migration Assay
3.9. Clonogenic Assay
3.10. Caspase-3 Enzymatic Activity: Evaluating Apoptosis-Induced Cell Death
3.11. Western Blot—Understanding the Mechanism of Tumor Growth Inhibition
3.12. In Vitro Tumor Simulation Model
3.12.1. Single-Dose Study
3.12.2. Multiple-Dose Study
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Formulation | Loading Method | % Drug Entrapment | % Drug Loading | Avg. Particle Size (nm) | Poly-Dispersity Index | Zeta Potential (mV) |
---|---|---|---|---|---|---|
Met pass | Passive | 5.2 ± 0.2 | 0.9 ± 0.03 | 136.3 ± 3.6 | 0.2 ± 0.1 | 1.2 ± 0.1 |
Met pH 3 | Active; pH 3.0 | 24.9 ± 3.9 | 4.4 ± 0.7 | 129.6 ± 10.1 | 0.2 ± 0.1 | −2.6 ± 0.8 |
Met pH 9 | Active; pH 9.0 | 9.9 ± 1.6 | 1.8 ± 0.3 | 136.3 ± 4.1 | 0.2 ± 0.1 | 0.6 ± 0.3 |
Met ND lipo | Drug loaded film | 58.2 ± 4.5 | 19.4 ± 1.5 | 102.3 ± 1.1 | 0.2 ± 0.0 | −1.2 ± 0.9 |
Met DO lipo | Drug loaded film | 65.6 ± 5.2 | 21.9 ± 1.7 | 98.2 ± 2.9 | 0.2 ± 0.0 | 39.9 ± 1.1 |
Release Model | Met ND lipo | Met DO lipo | ||
---|---|---|---|---|
Equation | r2 | Equation | r2 | |
Zero-order | Q = 0.1629 t + 0.2689 | 0.7901 | Q = 0.1597 t + 0.2282 | 0.8324 |
First order | ln(1−Q) = −0.3142 t + 2.0205 | 0.9989 | ln(1−Q) = −0.268 t + 2.0053 | 0.9984 |
Higuchi | Q = 0.4673 t1/2 + 0.0458 | 0.9546 | Q = 0.45 t1/2 + 0.0197 | 0.9712 |
Korsmeyer-Peppas | lnQ = −1.0357 lnt + 1.66 | 0.9300 | lnQ = −1.2276 lnt + 1.6213 | 0.9300 |
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Shukla, S.K.; Kulkarni, N.S.; Chan, A.; Parvathaneni, V.; Farrales, P.; Muth, A.; Gupta, V. Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer. Pharmaceutics 2019, 11, 559. https://doi.org/10.3390/pharmaceutics11110559
Shukla SK, Kulkarni NS, Chan A, Parvathaneni V, Farrales P, Muth A, Gupta V. Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer. Pharmaceutics. 2019; 11(11):559. https://doi.org/10.3390/pharmaceutics11110559
Chicago/Turabian StyleShukla, Snehal K., Nishant S. Kulkarni, Amanda Chan, Vineela Parvathaneni, Pamela Farrales, Aaron Muth, and Vivek Gupta. 2019. "Metformin-Encapsulated Liposome Delivery System: An Effective Treatment Approach against Breast Cancer" Pharmaceutics 11, no. 11: 559. https://doi.org/10.3390/pharmaceutics11110559