Formulation by Design of an Innovative Tea Tree Oil Nanoemulgel Incorporating Mupirocin for Enhanced Wound Healing Activity
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Designing the Experiment
2.3. The Formulation of Nanoemulsions
2.4. The Characterization of Mupirocin-Loaded NE Formulations
2.4.1. Particle Characterization
2.4.2. In Vitro Drug Release Study
2.5. The Formulation of Nanoemulgel
2.6. The Characterization of NE Formulation
2.6.1. Visual Inspection
2.6.2. pH Determination
2.6.3. Viscosity Measurement
2.6.4. Spreadability Test
2.6.5. Drug Content
2.7. The In Vitro Drug Release Study of NEG Formulation
2.8. Drug-Excipient Compatibility Studies (Fourier-Transform Infrared Spectroscopy (FTIR) Studies)
2.9. Scanning Electron Microscopy (SEM)
2.10. Stability Study
2.11. The Antibacterial Activity of Mupirocin-Loaded NEG against Different Bacterial Strains
2.12. Animals and Statement of Ethical Approval
2.13. Studies on Skin Irritation
2.14. The In Vivo Evaluation of Wound Healing Efficiency
2.14.1. Design of the Experiment
- Group I: rats were kept to heal without treatment (control group);
- Group II: rats were given commercial ointment (50 mg);
- Group III: rats were given blank NEG (50 mg);
- Group IV: rats were given mupirocin-loaded NEG (50 mg of 2% NEG) [38].
2.14.2. Excision Wound Establishment
2.14.3. Wound Area Measurement
2.15. Statistical Analysis
3. Results
3.1. Designing the Experiment
Fitting Models and Analyzing Statistical Data
3.2. The Characterization of Mupirocin-Loaded NE Formulations
3.2.1. The Effect of Selected Factors on Y1
3.2.2. The Impact of Selected Factors on Y2
3.3. Optimizing the Data
3.4. The Characterization of the Optimized Mupirocin NE
3.4.1. Visual Inspection
3.4.2. pH Determination
3.4.3. Viscosity Measurement
3.4.4. Spreadability Test
3.4.5. Drug Content
3.5. The In Vitro Drug Release Study of NEG Formulation
3.6. FTIR (Fourier-Transform Infrared Spectroscopy) Study
3.7. Scanning Electron Microscopy (SEM)
3.8. Stability Study
3.9. The Antibacterial Activity of Mupirocin-Loaded NEG against MRSA Bacterial Strain
3.10. Studies on Skin Irritation
3.11. The In Vivo Evaluation of Wound Healing Efficiency
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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Formula | Independent Variables | Dependent Variables | ||||
---|---|---|---|---|---|---|
A (%) | B (%) | C (%) | Particle Size (nm) | In Vitro Release (%) | PDI | |
F1 | 2.5 | 1 | 1.5 | 265 ± 3.2 | 50 ± 3.0 | 0.467 ± 0.061 |
F2 | 1.5 | 1 | 0.5 | 123 ± 2.0 | 75 ± 1.8 | 0.348 ± 0.034 |
F3 | 1.5 | 0.5 | 1.5 | 136 ± 2.5 | 73 ± 2.8 | 0.350 ± 0.049 |
F4 | 2 | 0.32 | 1 | 254 ± 3.4 | 53 ± 2.6 | 0.573 ± 0.048 |
F5 | 2 | 0.75 | 0.15 | 225 ± 1.9 | 55 ± 2.2 | 0.276 ± 0.013 |
F6 | 2 | 0.75 | 1 | 214 ± 3.0 | 59 ± 2.3 | 0.341 ± 0.032 |
F7 | 2 | 1.17 | 1 | 176 ± 2.9 | 65 ± 3.2 | 0.333 ± 0.031 |
F8 | 2.5 | 0.5 | 0.5 | 356 ± 4.5 | 42 ± 3.0 | 0.521 ± 0.024 |
F9 | 1.5 | 0.5 | 0.5 | 149 ± 2.5 | 69 ± 2.7 | 0.319 ± 0.019 |
F10 | 1.15 | 0.75 | 1 | 97 ± 2.0 | 81 ± 2.6 | 0.323 ± 0.035 |
F11 | 2 | 0.75 | 1 | 212 ± 3.2 | 60 ± 2.8 | 0.275 ± 0.010 |
F12 | 2 | 0.75 | 1.8 | 192 ± 1.7 | 62 ± 2.5 | 0.226 ± 0.007 |
F13 | 2.5 | 1 | 0.5 | 286 ± 3.6 | 47 ± 2.4 | 0.439 ± 0.018 |
F14 | 2 | 0.75 | 1 | 217 ± 3.5 | 57 ± 3.5 | 0.326 ± 0.012 |
F15 | 1.5 | 1 | 1.5 | 117 ± 2.1 | 79 ± 3.1 | 0.307 ± 0.021 |
F16 | 2.5 | 0.5 | 1.5 | 315 ± 4.7 | 45 ± 3.0 | 0.489 ± 0.018 |
F17 | 2.8 | 0.75 | 1 | 375 ± 3.4 | 40 ± 2.0 | 0.495 ± 0.010 |
Source | Y1 | Y2 | ||
---|---|---|---|---|
F-Value | p-Value | F-Value | p-Value | |
Model | 639.74 | <0.0001 * | 403.40 | <0.0001 * |
A | 5245.74 | <0.0001 * | 1126.16 | <0.0001 * |
B | 339.32 | <0.0001 * | 61.19 | <0.0001 * |
C | 72.07 | <0.0001 * | 22.84 | 0.0004 * |
AB | 37.14 | 0.0005 * | ||
AC | 12.21 | 0.0101 * | ||
BC | 4.81 | 0.0643 | ||
A² | 31.41 | 0.0008 * | ||
B² | 0.0157 | 0.9040 | ||
C2 | 3.60 | 0.0994 | ||
Lack of fit | 3.78 | 0.2221 | 0.8965 | 0.6378 |
R2 analysis | ||||
R² | 0.9988 | 0.9894 | ||
Adjusted R² | 0.9972 | 0.9869 | ||
Predicted R² | 0.9911 | 0.9820 | ||
Adequate precision | 85.9518 | 62.9684 | ||
Model | Quadratic | Linear | ||
Remark | Suggested | Suggested |
Selected Factor | Constraint | |
---|---|---|
Tea tree oil concentration (g) | In range | |
Tween 80 concentration (g) | In range | |
PEG 400 concentration (g) | In range | |
Response | Predicted values | Observed values |
Particle size (nm) | 120.26 ± 4.3 | 125.0 ± 3.6 |
In vitro release (%) | 77.75 ± 1.45 | 75.86 ± 1.5 |
Inhibition Zone Diameter (cm) | Bacterial Strain |
---|---|
MRSA | |
Blank NEG | 1.8 ± 0.10 |
Bactroban® ointment | 3.0 ± 0.15 * |
Mupirocin-loaded NEG | 3.4 ± 0.15 * ° |
Days | % of Unhealed Wound Lesions | |||
---|---|---|---|---|
Control Untreated | Marketed Ointment | Blank NEG | Mupirocin-Loaded NEG | |
0 | 102.8 ± 4.7 | 101 ± 5.3 | 102.8 ± 5.7 | 102.8 ± 5.7 |
4 | 97.3 ± 5.1 | 73.3 ± 1.4 * ° | 80 ± 4.0 * $ | 61.63 ± 3.2 * ° $ |
7 | 94.0 ± 4.5 | 54.3 ± 3.4 * ° | 72.53 ± 1.53 * $ | 31.67 ± 5.1 * ° $ |
14 | 90.3 ± 4.5 | 36.67 ± 3.0 * ° | 50.0 ± 1.0 * $ | 10.27 ± 2.0 * ° $ |
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Bujubarah, M.M.; Elsewedy, H.S.; Shehata, T.M.; Soliman, W.E. Formulation by Design of an Innovative Tea Tree Oil Nanoemulgel Incorporating Mupirocin for Enhanced Wound Healing Activity. Appl. Sci. 2023, 13, 13244. https://doi.org/10.3390/app132413244
Bujubarah MM, Elsewedy HS, Shehata TM, Soliman WE. Formulation by Design of an Innovative Tea Tree Oil Nanoemulgel Incorporating Mupirocin for Enhanced Wound Healing Activity. Applied Sciences. 2023; 13(24):13244. https://doi.org/10.3390/app132413244
Chicago/Turabian StyleBujubarah, Mahdi M., Heba S. Elsewedy, Tamer M. Shehata, and Wafaa E. Soliman. 2023. "Formulation by Design of an Innovative Tea Tree Oil Nanoemulgel Incorporating Mupirocin for Enhanced Wound Healing Activity" Applied Sciences 13, no. 24: 13244. https://doi.org/10.3390/app132413244
APA StyleBujubarah, M. M., Elsewedy, H. S., Shehata, T. M., & Soliman, W. E. (2023). Formulation by Design of an Innovative Tea Tree Oil Nanoemulgel Incorporating Mupirocin for Enhanced Wound Healing Activity. Applied Sciences, 13(24), 13244. https://doi.org/10.3390/app132413244