Phosphatidylcholine-Based Nanoemulsions for Paclitaxel and a P-Glycoprotein Inhibitor Delivery and Breast Cancer Intraductal Treatment
Abstract
:1. Introduction
2. Results
2.1. Nanoemulsion Development, Composition Selection, and Cytotoxicity
2.1.1. Influence of the Oil Phase on NE Characteristics: Effects of PA and Tributyrin
2.1.2. Influence of HA Incorporation on NE Characteristics
2.1.3. Characterization of Selected Formulations
2.1.4. Influence of Nanoemulsion Composition on Its Cytotoxicity
2.2. Influence of Paclitaxel and Elacridar Incorporation on Nanoemulsion Characteristics
2.3. P-Glycoprotein Inhibition Assay
2.4. Cytotoxicity Evaluation of the Drug-Loaded NETri
2.4.1. Cytotoxicity in Cell Monolayers
2.4.2. Cytotoxicity in Spheroids
2.5. In Vivo Mammary Retention of a Fluorescent Marker
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Nanoemulsion Development
4.2.1. Influence of Oil Phase on NE Formation
4.2.2. Influence of the Aqueous Phase on NE Formation
4.3. Drug Incorporation, Short-Term Stability and Release
4.4. Cytotoxicity Assays: 2D and 3D Models
4.4.1. Cytotoxicity Evaluation in Cell Monolayers (2D Model)
4.4.2. Cytotoxicity Evaluation in Spheroids (3D Model)
4.5. Glycoprotein-P Inhibition Assay
4.6. In Vivo Mammary Retention of a Fluorescent Marker Mediated by the Selected Nanoemulsion
4.7. Statistical Analyses
5. Conclusions
6. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nanoemulsion | Oil Phase/Drug Concentration | Size (d.nm) | PDI | Zeta Potential (mV) |
---|---|---|---|---|
NE (no HA) | Tricaprylin | 164.3 ± 7.8 | 0.178 ± 0.02 | −23.8 ± 2.8 |
NETri (no HA) | Tricaprylin + tributyrin (1%) | 100.89 ± 1.1 | 0.114 ± 0.04 | −41.7 ± 1.8 |
Tricaprylin + tributyrin (2.5%) | - | - | - | |
NEPA (no HA) | Tricaprylin + PA (0.5%) | 175.1 ± 1.8 | 0.204 ± 0.11 | −27.2 ± 1.2 |
Tricaprylin + PA (1%) | 139.4 ± 0.9 | 0.192 ± 0.01 | −12.1 ± 0.7 | |
Tricaprylin + PA (2.5%) | 155.2 ± 1.7 | 0.170 ± 0.04 | −17.7 ± 2.2 | |
Tricaprylin + PA (5%) | - | - | - | |
E-NETri (with 0.25% HA) | Tricaprylin + tributyrin (1%) 0.1% E | 608.1 ± 0.4 | 0.327 ± 0.01 | −19.9 ± 3.1 |
Tricaprylin + tributyrin (1%) (0.07% E) | 202.9 ± 0.7 | 0.197 ± 0.03 | −17.5 ± 1.8 | |
PE-NETri (with 0.25% HA) | Tricaprylin + tributyrin (1%) 0.07% E + 1% P | 228.9 ± 1.0 | 0.459 ± 0.01 | −19.0 ± 5.9 |
Tricaprylin + tributyrin (1%) 0.07% E + 0.5% P | 114.6 ± 1.2 | 0.292 ± 0.01 | −32.4 ± 0.28 | |
E-NEPA (with 0.25% HA) | Tricaprylin + PA (0.5%) 0.1% E | 329.2 ± 8.7 | 0.216 ± 0.02 | −11.4 ± 0.2 |
Tricaprylin + PA (0.5%) 0.07% E | 138.7 ± 1.9 | 0.183 ± 0.11 | −15.1 ± 1.5 | |
PE-NEPA (with 0.25% HA) | Tricaprylin + PA (0.5%) (0.07% E + 1% P) | 216.0 ± 14.8 | 0.413 ± 0.06 | −34.2 ± 6.7 |
Tricaprylin + PA (0.5%) (0.07% E + 0.5% P) | 134.2 ± 3.8 | 0.293 ± 0.01 | −26.0 ± 1.4 |
MCF-7 | MDA-MB-231 | |||
---|---|---|---|---|
IC50 | mg/mL of NE | µM of P | mg/mL of NE | µM of P |
U-NE without HA | - | - | 15.5 | - |
U-NE | - | - | 6.6 | - |
NETri | 9.7 | - | 8.2 | - |
NEPA | 12.6 | - | 9.7 | - |
P-Sol | - | 78.8 | - | 61.8 |
PE-Sol | - | 66.0 | - | 62.4 |
P-NETri | 4.7 | 27.4 | 0.9 | 5.0 |
PE-NETri | 2.9 | 17.1 | 0.3 | 1.7 |
MCF-7 | MDA-MB-231 | |||
---|---|---|---|---|
IC50 | mg/mL of NE | µM of P | mg/mL of NE | µM of P |
NETri | - | - | - | - |
PE-Sol | - | - | - | - |
P-NETri | 6.6 | 38.5 | 11.1 | 64.8 |
PE-NETri | 3.9 | 23.1 | 3.4 | 19.7 |
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Salata, G.C.; Lopes, L.B. Phosphatidylcholine-Based Nanoemulsions for Paclitaxel and a P-Glycoprotein Inhibitor Delivery and Breast Cancer Intraductal Treatment. Pharmaceuticals 2022, 15, 1110. https://doi.org/10.3390/ph15091110
Salata GC, Lopes LB. Phosphatidylcholine-Based Nanoemulsions for Paclitaxel and a P-Glycoprotein Inhibitor Delivery and Breast Cancer Intraductal Treatment. Pharmaceuticals. 2022; 15(9):1110. https://doi.org/10.3390/ph15091110
Chicago/Turabian StyleSalata, Giovanna Cassone, and Luciana B. Lopes. 2022. "Phosphatidylcholine-Based Nanoemulsions for Paclitaxel and a P-Glycoprotein Inhibitor Delivery and Breast Cancer Intraductal Treatment" Pharmaceuticals 15, no. 9: 1110. https://doi.org/10.3390/ph15091110
APA StyleSalata, G. C., & Lopes, L. B. (2022). Phosphatidylcholine-Based Nanoemulsions for Paclitaxel and a P-Glycoprotein Inhibitor Delivery and Breast Cancer Intraductal Treatment. Pharmaceuticals, 15(9), 1110. https://doi.org/10.3390/ph15091110