Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Vesicle Preparation
2.3. Vesicle Characterization
2.4. 31P-NMR Measurements
2.5. Small- and Wide-Angle X-ray Scattering
2.6. In Vitro Skin Delivery Studies
2.7. Cell Viability Assay
2.8. In Vitro Antifungal Activity
2.9. In Vivo Antifungal Activity
2.10. Microscopic Visualization of Skin Infected with C. albicans
2.11. Statistical Data Analysis
3. Results
3.1. Characterization of Three-Dimensionally-Structured Hybrid Vesicles
3.2. 31P-NMR Measurements and Small- and Wide-Angle X-ray Scattering (SAXS and WAXS)
3.3. In Vitro Skin Permeation Studies
3.4. In Vitro Cytotoxicity of Clotrimazole Loaded Hybrid Vesicles
3.5. In Vitro Antifungal Susceptibility Test
3.6. In Vivo Antifungal Activity Evaluation
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Lecithin (mg/mL) | Clotrimazole (mg/mL) | Glycerol (mL) | Ethanol (mL) | Water (mL) | |
---|---|---|---|---|---|
59:2 vesicles | 90 | 10 | 0.59 | 0.39 | 0.02 |
53:10 vesicles | 90 | 10 | 0.53 | 0.37 | 0.10 |
69:2 vesicles | 90 | 10 | 0.69 | 0.29 | 0.02 |
63:10 vesicles | 90 | 10 | 0.63 | 0.27 | 0.10 |
Mean Diameter (nm) | PI | Zeta Potential (mV) | EE (%) | |
---|---|---|---|---|
Empty 59:2 vesicles | 171 ± 2 | 0.38 | −55 ± 2 | - |
Empty 53:10 vesicles | 244 ± 13 | 0.43 | −68 ± 3 | - |
Empty 69:2 vesicles | 169 ± 2 | 0.30 | −65 ± 1 | - |
Empty 63:10 vesicles | 221 ± 3 | 0.38 | −66 ± 3 | - |
Clotrimazole 59:2 vesicles | 96 ± 2 | 0.26 | −64 ± 58 | 96 ± 5 |
Clotrimazole 53:10 vesicles | 186 ± 6 | 0.29 | −59 ± 2 | 84 ± 5 |
Clotrimazole 69:2 vesicles | 129 ± 7 | 0.28 | −77 ± 1 | 98 ± 8 |
Clotrimazole 63:10 vesicles | 140 ± 11 | 0.23 | −61 ± 1 | 81 ± 7 |
zH | σH | dB | |
---|---|---|---|
Empty liposomes | 18.7 ± 0.1 | 3.4 ± 0.1 | 51.0 ± 0.6 |
Empty 59:2 vesicles | 16.9 ± 0.2 | 6.5 ± 0.1 | 59.9 ± 0.8 |
Empty 53:10 vesicles | 16.8 ± 0.2 | 6.7 ± 0.1 | 60.4 ± 0.8 |
Empty 69:2 vesicles | 19.0 ± 0.1 | 4.7 ± 0.2 | 56.8 ± 1.0 |
Empty 63:10 vesicles | 20.4 ± 0.1 | 4.8 ± 0.2 | 60.0 ± 1.0 |
Clotrimazole 59:2 vesicles | 17.7 ± 0.2 | 6.3 ± 0.2 | 60.6 ± 1.2 |
Clotrimazole 53:10 vesicles | 17.4 ± 0.2 | 6.8 ± 0.2 | 62.0 ± 1.2 |
Clotrimazole 69:2 vesicles | 18.5 ± 0.2 | 4.5 ± 0.2 | 55.0 ± 1.2 |
Clotrimazole 63:10 vesicles | 18.9 ± 0.1 | 4.1 ± 0.2 | 54.2 ± 1.0 |
MIC (µg/mL) | MBC (µg/mL) | MBIC (µg/mL) | |
---|---|---|---|
Clotrimazole 59:2 vesicles | 2.5 | 2.5 | <0.002 |
Clotrimazole 53:10 vesicles | >5 | >5 | 5 |
Clotrimazole 69:2 vesicles | >5 | >5 | 5 |
Clotrimazole 63:10 vesicles | 1.25 | 1.25 | 0.004 |
Canesten® | NE | NE | NE |
Empty 59:2 vesicles | >5 | >5 | >5 |
Empty 53:10 vesicles | >5 | >5 | >5 |
Empty 69:2 vesicles | >5 | >5 | >5 |
Empty 63:10 vesicles | >5 | >5 | >5 |
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Manca, M.L.; Usach, I.; Peris, J.E.; Ibba, A.; Orrù, G.; Valenti, D.; Escribano-Ferrer, E.; Gomez-Fernandez, J.C.; Aranda, F.J.; Fadda, A.M.; et al. Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis. Pharmaceutics 2019, 11, 263. https://doi.org/10.3390/pharmaceutics11060263
Manca ML, Usach I, Peris JE, Ibba A, Orrù G, Valenti D, Escribano-Ferrer E, Gomez-Fernandez JC, Aranda FJ, Fadda AM, et al. Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis. Pharmaceutics. 2019; 11(6):263. https://doi.org/10.3390/pharmaceutics11060263
Chicago/Turabian StyleManca, Maria Letizia, Iris Usach, José Esteban Peris, Antonella Ibba, Germano Orrù, Donatella Valenti, Elvira Escribano-Ferrer, Juan Carmelo Gomez-Fernandez, Francisco José Aranda, Anna Maria Fadda, and et al. 2019. "Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis" Pharmaceutics 11, no. 6: 263. https://doi.org/10.3390/pharmaceutics11060263
APA StyleManca, M. L., Usach, I., Peris, J. E., Ibba, A., Orrù, G., Valenti, D., Escribano-Ferrer, E., Gomez-Fernandez, J. C., Aranda, F. J., Fadda, A. M., & Manconi, M. (2019). Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis. Pharmaceutics, 11(6), 263. https://doi.org/10.3390/pharmaceutics11060263