Development of an Antiviral Ion-Activated In Situ Gel Containing 18β-Glycyrrhetinic Acid: A Promising Alternative against Respiratory Syncytial Virus
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Preparation of GA-Loaded In Situ Gelling Formulations
Preparation of In Situ Gelling Systems Using Only Gellan Gum
Preparation of In Situ Gelling Systems Using Combined Polymers
2.2.2. Characterization of GA-Loaded In Situ Gelling Formulations
Gelation Capacity of In Situ Gelling Formulations with/without Mucoadhesive Polymers
Rheological Evaluation
Mechanical Characteristics of In Situ Gelling Formulations
In Situ Gelling Formulation–Mucin Interaction Study
Ex Vivo Mucoadhesive Strength Test
Sprayability Analysis
Quantitative Determination of 18β-Glycyrrhetinic Acid
Active Substance Content Determination
Fourier Transform Infrared Spectrometry (FTIR) Studies
In Vitro Release Study
Physicochemical Stability
2.2.3. Cell Culture Studies
Cells and Virus
Cytotoxicity Assay
3. Results and Discussion
3.1. Optimization and Characterization of GA-Loaded In Situ Gelling Formulations
3.1.1. Gelation Capacity of In Situ Gelling Formulations
3.1.2. Rheological Evaluation
3.1.3. Mechanical Characteristics of In Situ Gelling Formulations
3.1.4. In Situ Gelling Formulation–Mucin Interaction Study
3.1.5. Ex Vivo Mucoadhesive Strength Test
3.1.6. Sprayability
3.1.7. Quantitative Determination of 18β-Glycyrrhetinic Acid
3.1.8. Active Substance Content Determination
3.1.9. Fourier Transform Infrared Spectrometry (FTIR) Studies
3.1.10. In Vitro Release Study
3.1.11. Physicochemical Stability
3.2. Cell Culture Studies
3.2.1. Cytotoxicity Assay
3.2.2. Virus Titration
3.2.3. Antiviral Activity Assay
4. 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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Ingredients | Composition (% w/w) | ||||||||
---|---|---|---|---|---|---|---|---|---|
DGG | 0.2 | 0.3 | 0.4 | 0.5 | 0.6 | 0.7 | 0.8 | 0.9 | 1 |
GA | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
Dexpanthenol | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
Glycerin | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Benzalkonium chloride | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 |
Distilled water | 98.48 | 98.38 | 98.28 | 98.18 | 98.08 | 97.98 | 97.88 | 97.78 | 97.68 |
Ingredients | Composition (% w/w) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
DGG | 0.4 | 0.5 | 0.6 | 0.4 | 0.5 | 0.6 | 0.4 | 0.5 | 0.6 | 0.4 | 0.5 | 0.6 |
GA | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 | 0.1 |
Xanthan gum | 0.5 | 0.5 | 0.5 | - | - | - | - | - | - | - | - | - |
HPMC | - | - | - | 0.5 | 0.5 | 0.5 | - | - | - | - | - | - |
Na-CMC | - | - | - | - | - | - | 0.5 | 0.5 | 0.5 | - | - | - |
Carbopol® 974P NF | - | - | - | - | - | - | - | - | - | 0.5 | 0.5 | 0.5 |
Dexpanthenol | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 | 0.2 |
Glycerin | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Benzalkonium chloride | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 | 0.02 |
Distilled water | 97.78 | 97.68 | 97.58 | 97.78 | 97.68 | 97.58 | 97.78 | 97.68 | 97.58 | 97.78 | 97.68 | 97.58 |
Ingredients | Composition (% w/w) | |||
---|---|---|---|---|
DGG | 0.5 | 0.5 | 0.5 | 0.5 |
GA | 0.1 | 0.1 | 0.1 | 0.1 |
Na-CMC | 0.1 | 0.3 | 0.5 | 0.7 |
Dexpanthenol | 0.2 | 0.2 | 0.2 | 0.2 |
Glycerin | 1 | 1 | 1 | 1 |
Benzalkonium chloride | 0.02 | 0.02 | 0.02 | 0.02 |
Distilled water | 98.08 | 97.88 | 97.68 | 97.48 |
Formulation | ηp | ηm | ηt | ηb | Fb (Pa) |
---|---|---|---|---|---|
DGG 0.4% − HPMC | 125.68 ± 2.84 | 13.95 ± 0.32 | 238.13 ± 11.25 | 98.50 ± 2.76 | 3.94 ± 0.45 |
DGG 0.5% − HPMC | 168.68 ± 6.23 | 13.95 ± 0.32 | 294.35 ± 14.98 | 111.73 ± 4.87 | 4.47 ± 0.87 |
DGG 0.6% − HPMC | 251.36 ± 16.89 | 13.95 ± 0.32 | 343.96 ± 10.62 | 78.65 ± 1.34 | 3.15 ± 0.23 |
DGG 0.4% − Na-CMC | 55.59 ± 2.38 | 13.95 ± 0.32 | 191.82 ± 7.94 | 122.28 ± 8.98 | 4.89 ± 0.98 |
DGG 0.5% − Na-CMC | 72.48 ± 1.68 | 13.95 ± 0.32 | 321.08 ± 9.15 | 234.65 ± 11.85 | 9.39 ± 0.34 |
DGG 0.6% − Na-CMC | 74.01 ± 2.24 | 13.95 ± 0.32 | 327.43 ± 12.18 | 239.46 ± 10.37 | 9.58 ± 1.36 |
DGG 0.4% − xanthan gum | 99.22 ± 3.34 | 13.95 ± 0.32 | 317.51 ± 15.64 | 204.34 ± 8.82 | 8.17 ± 1.67 |
DGG 0.5% − xanthan gum | 148.83 ± 5.75 | 13.95 ± 0.32 | 317.04 ± 10.21 | 154.26 ± 2.75 | 6.17 ± 1.43 |
DGG 0.6% − xanthan gum | 188.52 ± 4.90 | 13.95 ± 0.32 | 317.51 ± 6.86 | 115.04 ± 9.46 | 4.60 ± 0.24 |
Formulation | ηp | ηm | ηt | ηb | Fb (Pa) |
---|---|---|---|---|---|
DGG 0.5% − Na-CMC 0.1% | 20.28 ± 0.33 | 16.51 ± 0.49 | 298.84 ± 18.36 | 262.06 ± 13.36 | 8.91 ± 1.21 |
DGG 0.5% − Na-CMC 0.3% | 54.28 ± 0.71 | 16.51 ± 0.49 | 315.03 ± 18.39 | 244.23 ± 11.36 | 8.30 ± 0.56 |
DGG 0.5% − Na-CMC 0.5% | 74.23 ± 3.16 | 16.51 ± 0.49 | 371.08 ± 19.17 | 280.34 ± 16.23 | 9.53 ± 0.78 |
DGG 0.5% − Na-CMC 0.7% | 116.41 ± 5.82 | 16.51 ± 0.49 | 371.37 ± 15.89 | 238.44 ± 10.20 | 8.11 ± 0.43 |
Formulation | Adhesion Strength (g) |
---|---|
DGG 0.5% − Na-CMC 0.1% | 14.33 ± 8.40 |
DGG 0.5% − Na-CMC 0.3% | 15.67 ± 5.20 |
DGG 0.5% − Na-CMC 0.5% | 19.67 ± 5.90 |
DGG 0.5% − Na-CMC 0.7% | 27.67 ± 6.80 |
Formulation | T1 | T7 | T14 | ||
---|---|---|---|---|---|
Mean ± SD | Mean ± SD | Weight Deviation (%) | Mean ± SD | Weight Deviation (%) | |
DGG 0.5% − Na-CMC 0.1% | 0.323 ± 0.003 | 0.319 ± 0.002 | 1.24 | 0.320 ± 0.003 | 0.93 |
DGG 0.5% − Na-CMC 0.3% | 0.319 ± 0.002 | 0.326 ± 0.001 | 2.19 | 0.323 ± 0.002 | 1.25 |
DGG 0.5% − Na-CMC 0.5% | 0.306 ± 0.001 | 0.299 ± 0.002 | 2.29 | 0.302 ± 0.001 | 1.30 |
DGG 0.5% − Na-CMC 0.7% | 0.299 ± 0.003 | 0.287 ± 0.001 | 4.01 | 0.294 ± 0.001 | 1.67 |
Cytotoxicity | ||
---|---|---|
Sample Type | MNTC a (µg/mL) | CC50 b (µg/mL) |
GA | 8.33 | 47.59 |
GA in situ gelling formulation | 4.16 | 15.29 |
Placebo in situ gelling formulation | 4.16 | 14.84 |
Ribavirin | 0.98 | 117.00 |
Sample Type | Simultaneous | Pre-Infection | ||
---|---|---|---|---|
EC50 a (µg/mL) | SI b | EC50 a (µg/mL) | SI b | |
GA | 0.435 | 109.65 | 0.115 | 415.00 |
GA in situ gelling formulation | 0.050 | 306.00 | 0.154 | 100.00 |
Placebo in situ gelling formulation | 0.790 | 18.83 | 2.005 | 7.40 |
Ribavirin | 4.189 | 28.00 |
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Özkan, B.; Altuntaş, E.; Ünlü, Ü.; Doğan, H.H.; Özsoy, Y.; Çakır Koç, R. Development of an Antiviral Ion-Activated In Situ Gel Containing 18β-Glycyrrhetinic Acid: A Promising Alternative against Respiratory Syncytial Virus. Pharmaceutics 2023, 15, 2055. https://doi.org/10.3390/pharmaceutics15082055
Özkan B, Altuntaş E, Ünlü Ü, Doğan HH, Özsoy Y, Çakır Koç R. Development of an Antiviral Ion-Activated In Situ Gel Containing 18β-Glycyrrhetinic Acid: A Promising Alternative against Respiratory Syncytial Virus. Pharmaceutics. 2023; 15(8):2055. https://doi.org/10.3390/pharmaceutics15082055
Chicago/Turabian StyleÖzkan, Burcu, Ebru Altuntaş, Ümmühan Ünlü, Hasan Hüseyin Doğan, Yıldız Özsoy, and Rabia Çakır Koç. 2023. "Development of an Antiviral Ion-Activated In Situ Gel Containing 18β-Glycyrrhetinic Acid: A Promising Alternative against Respiratory Syncytial Virus" Pharmaceutics 15, no. 8: 2055. https://doi.org/10.3390/pharmaceutics15082055
APA StyleÖzkan, B., Altuntaş, E., Ünlü, Ü., Doğan, H. H., Özsoy, Y., & Çakır Koç, R. (2023). Development of an Antiviral Ion-Activated In Situ Gel Containing 18β-Glycyrrhetinic Acid: A Promising Alternative against Respiratory Syncytial Virus. Pharmaceutics, 15(8), 2055. https://doi.org/10.3390/pharmaceutics15082055