Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of SLNs and Vectors
2.3. Size and Zeta Potential of SLNs and Vectors
2.4. Adhesion Test
2.5. Rheology Studies
2.6. pH Measurement
2.7. In Vitro Studies
2.7.1. Transfection Efficacy of the Vectors Containing the Plasmid pUNO1-hIL10
2.7.2. In Vitro Cell Viability
2.8. In Vivo Studies
2.8.1. Detection of CD44 Receptor in Cornea from Wild Type and IL-10 KO Mice
2.8.2. Corneal Localization of the Vectors
2.8.3. In Vivo Transfection Studies
Topical Administration
Evaluation of Gene Expression
Structural Analysis of the Cornea
2.9. Statistical Analysis
3. Results
3.1. Size and Zeta Potential of SLNs and Vectors
3.2. Adhesion Test: Flow Rates
3.3. Rheology Studies
3.4. pH Values
3.5. In Vitro Studies
3.5.1. Transfection Efficacy of the Vectors Containing the Plasmid pUNO1-hIL10
3.5.2. In Vitro Cell Viability
3.6. In Vivo Studies
3.6.1. Detection of CD44
3.6.2. Corneal Localization of the Vectors
3.6.3. In Vivo Transfection with the Vectors Containing the Plasmid pcDNA3-EGFP
3.6.4. In Vivo Transfection with the Vectors Containing the pUNO1-hIL10 Plasmid
3.6.5. Structural Analysis of the Cornea
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Name of the Complex | Weight Ratio |
---|---|
DX-SLNEE | DX:P:DNA:SLNEE 1:2:1:5 |
HA-SLNEE | HA:P:DNA:SLNEE 0.5:2:1:2 |
DNA-SLNC | DNA:SLNC 1:10 |
HA-SLNC | HA:P:DNA:SLNC 0.5:1:1:10 |
Size (nm) | PDI | Zeta Potential (mV) | |
---|---|---|---|
SLNEE | 202.2 ± 28.2 * | 0.25 ± 0.01 | +51.3 ± 2.2 |
HA-SLNEE | |||
pcDNA3-EGFP | 204.9 ± 15.0 | 0.18 ± 0.07 | +29.2 ± 3.1 |
pUNO1-hIL10 | 266.1 ± 11.4 | 0.34 ± 0.03 | +29.7 ± 1.2 |
DX-SLNEE | |||
pcDNA3-EGFP | 177.3 ± 23.2 # | 0.33 ± 0.06 | +39.3 ± 1.5 # |
pUNO1-hIL10 | 159.4 ± 4.9 ‡ | 0.27 ± 0.02 | +34.1 ± 0.6 ‡ |
SLNC | 453.9 ± 13.6 | 0.26 ± 0.03 | +33.8 ± 2.5 |
DNA-SLNC | |||
pcDNA3-EGFP | 404.1 ± 7.2 # | 0.27 ± 0.02 | +20.8 ± 1.5 |
pUNO1-hIL10 | 447.9 ± 17.0 ‡ | 0.29 ± 0.04 | +14.7 ± 0.7 & |
HA-SLNC | |||
pcDNA3-EGFP | 368.5 ± 7.4 | 0.24 ± 0.02 | +21.9 ± 0.9 |
pUNO1-hIL10 | 374.7 ± 14.5 | 0.29 ± 0.02 | +15.8 ± 2.4 & |
Sample | R2 | Viscosity 10 s−1 (mPa·s) | Viscosity 500 s−1 (mPa·s) | K (Pa·sn) | n |
---|---|---|---|---|---|
Water | 0.9947 | 0.73 | 0.87 | 0.001 | 1.065 |
Plasmid solution | 0.9847 | 0.78 | 0.98 | 0.001 | 1.11 |
Plasmid solution + PVA | 0.9995 | 2.14 | 1.91 | 0.002 | 0.976 |
HA-SLNEE | 0.9588 | 18.40 | 2.92 | 0.067 | 0.519 |
HA-SLNEE + PVA | 0.9592 | 8.26 | 2.38 | 0.015 | 0.681 |
DX-SLNEE | 0.9921 | 1.60 | 1.00 | 0.002 | 0.876 |
DX-SLNEE + PVA | 0.9969 | 3.31 | 2.16 | 0.004 | 0.879 |
HA-SLNC | 0.8642 | 10.70 | 1.75 | 0.028 | 0.525 |
HA-SLNC + PVA | 0.9995 | 3.29 | 3.08 | 0.003 | 0.989 |
Sample | pH |
---|---|
Plasmid solution | 7.4 ± 0.13 |
Plasmid solution + PVA | 7.3 ± 0.13 |
HA-SLNEE | 7.3 ± 0.03 |
HA-SLNEE + PVA | 7.2 ± 0.01 |
DX-SLNEE | 7.5 ± 0.10 |
DX-SLNEE + PVA | 7.0 ± 0.18 |
HA-SLNC | 4.0 ± 0.07 |
HA-SLNC + PVA | 4.3 ± 0.11 |
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Vicente-Pascual, M.; Gómez-Aguado, I.; Rodríguez-Castejón, J.; Rodríguez-Gascón, A.; Muntoni, E.; Battaglia, L.; del Pozo-Rodríguez, A.; Solinís Aspiazu, M.Á. Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production. Pharmaceutics 2020, 12, 584. https://doi.org/10.3390/pharmaceutics12060584
Vicente-Pascual M, Gómez-Aguado I, Rodríguez-Castejón J, Rodríguez-Gascón A, Muntoni E, Battaglia L, del Pozo-Rodríguez A, Solinís Aspiazu MÁ. Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production. Pharmaceutics. 2020; 12(6):584. https://doi.org/10.3390/pharmaceutics12060584
Chicago/Turabian StyleVicente-Pascual, Mónica, Itziar Gómez-Aguado, Julen Rodríguez-Castejón, Alicia Rodríguez-Gascón, Elisabetta Muntoni, Luigi Battaglia, Ana del Pozo-Rodríguez, and María Ángeles Solinís Aspiazu. 2020. "Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production" Pharmaceutics 12, no. 6: 584. https://doi.org/10.3390/pharmaceutics12060584
APA StyleVicente-Pascual, M., Gómez-Aguado, I., Rodríguez-Castejón, J., Rodríguez-Gascón, A., Muntoni, E., Battaglia, L., del Pozo-Rodríguez, A., & Solinís Aspiazu, M. Á. (2020). Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production. Pharmaceutics, 12(6), 584. https://doi.org/10.3390/pharmaceutics12060584