Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of the Gel
2.3. Physicochemical Characterization of the MA Gel
2.3.1. Morphological Analysis
2.3.2. Swelling and Degradation Tests
2.3.3. Water Loss Due to Drying
2.3.4. Porosity Study
2.4. Stability Studies
2.5. Rheological Studies
2.6. Spreadability Test
2.7. In Vitro Release Studies
2.8. Ex Vivo Permeation Studies
2.9. In Vivo Tolerance Study
2.10. Parasite Strains and Cultures
2.11. In Vitro Cytotoxicity Assay
2.12. In Vitro Anti-Leishmanial Activity against Promastigotes
2.13. In Vitro Anti-Leishmanial Activity against Intracellular Amastigotes
2.14. Statistical Analysis
3. Results
3.1. Physicochemical Characterization of the MA Gel
3.2. Drug Quantification and Stability Studies
3.3. Rheological Studies
3.4. Spreadability Test
3.5. In Vitro Release Studies
3.6. Ex Vivo Permeation Studies
3.7. In Vivo Tolerance Study
3.8. In Vitro Cytotoxicity Assay
3.9. Anti-Leishmanial In Vitro Activity against Promastigotes
3.10. Anti-Leishmanial In Vitro Activity against Intracellular Amastigotes
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Formulations | SbV (µg/mL) ± SD | |||
---|---|---|---|---|
t0 | t180 RT | t180 37 °C | t180 4 °C | |
MA solution | 79,659.92 ± 1023.45 | |||
MA gel | 57,936.62 ± 894.92 | 57,436.62 ± 854.92 | 58,575.93 ± 654.07 | 59,255.83 ± 524.49 |
Assay | MA Solution | MA Gel | ||
---|---|---|---|---|
Non-Damaged Skin | Damaged Skin | Non-Damaged Skin | Damaged Skin | |
Permeation (µg/cm2) ± SD | 2966.50 ± 562.37 | 121.00 ± 59.45 | 1217.53 ± 279.41 | 774.81 ± 179.63 |
Retention in skin (µg/g/cm2) ± SD | 51,672.84 ± 8964.28 | 2057.47 ± 381.67 | 71,043.69 ± 10,641.57 | 10,728.23 ± 2254.61 |
Formulations (µg/mL SbV) | IC50 (µg/mL SbV ± SD) | SI | CC50 (µg/mL SbV ± SD) | |||
---|---|---|---|---|---|---|
Promastigotes | Amastigotes | SIRAW | SIJ774 | RAW 264.7 | J774A.1 | |
MA solution | >750 (* na) | 57.35 ± 2.76 | 6.66 | 6.37 | 381.76 ± 94.74 | 365.14 ± 165.26 |
MA gel | 633.15 ± 43.26 (* na) | 15.76 ± 4.81 | 14.19 | 14.03 | 223.66 ± 46.82 | 221.05 ± 65.41 |
Excipients | IC50 (µg/mL ± SD) | SI | CC50 (µg/mL ± SD) | |||
---|---|---|---|---|---|---|
Promastigotes | Amastigotes | SIRAW | SIJ774 | RAW 264.7 | J774A.1 | |
Gelling agents (375–0.37 µg/mL) | >375 | 20.39 ± 5.43 | 6.57 | 6.13 | 134.00 ± 42.57 | 125.00 ± 20.80 |
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Berenguer, D.; Sosa, L.; Alcover, M.; Sessa, M.; Halbaut, L.; Guillén, C.; Fisa, R.; Calpena-Campmany, A.C.; Riera, C. Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis. Pharmaceutics 2019, 11, 613. https://doi.org/10.3390/pharmaceutics11110613
Berenguer D, Sosa L, Alcover M, Sessa M, Halbaut L, Guillén C, Fisa R, Calpena-Campmany AC, Riera C. Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis. Pharmaceutics. 2019; 11(11):613. https://doi.org/10.3390/pharmaceutics11110613
Chicago/Turabian StyleBerenguer, Diana, Lilian Sosa, Magdalena Alcover, Marcella Sessa, Lyda Halbaut, Carme Guillén, Roser Fisa, Ana Cristina Calpena-Campmany, and Cristina Riera. 2019. "Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis" Pharmaceutics 11, no. 11: 613. https://doi.org/10.3390/pharmaceutics11110613
APA StyleBerenguer, D., Sosa, L., Alcover, M., Sessa, M., Halbaut, L., Guillén, C., Fisa, R., Calpena-Campmany, A. C., & Riera, C. (2019). Development and Characterization of a Semi-Solid Dosage Form of Meglumine Antimoniate for Topical Treatment of Cutaneous Leishmaniasis. Pharmaceutics, 11(11), 613. https://doi.org/10.3390/pharmaceutics11110613