Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Construction of Phase Diagram to Identify Factors Affecting Micro- or Nanoemulsion Formulation
2.2.1. Effects of HLB Value of Surfactant and Single-Tail Co-Surfactant System
2.2.2. Effect of Co-Solvent
2.2.3. Effect of Co-Surfactant Hydrocarbon Tails
2.2.4. Design of Experiment Program (DoE) with Design Expert® for Low Surfactant Micro- or Nanoemulsions
2.3. Characterization of Studied Colloidal Dispersion
2.3.1. Polarized Light Microscopy
2.3.2. Droplet Size and Distribution Determination
2.3.3. Turbidity Measurement
2.3.4. Electrical Conductivity
2.3.5. Viscosity Measurement
2.4. Determination of Tripeptide-3 with High-Performance Liquid Chromatography (HPLC)
2.5. Stability Tests of Colloidal Dispersion
2.5.1. Stress Testing by Heating–Cooling Cycles
2.5.2. Stress Testing by Freeze–Thaw Cycles
2.5.3. Stress Testing by Centrifugation
2.5.4. pH Challenge Test
2.6. Skin Permeation Study
2.7. Skin Irritation Test and Efficacy Test of Tripeptide-3 Optimized Formulation in Human Volunteers
2.7.1. Ethics Consideration
2.7.2. Human Volunteers
2.7.3. Skin Irritation Test
2.7.4. Efficacy Test
2.8. Statistical Evaluation
3. Results & Discussion
3.1. Factors Affecting Micro- or Nanoemulsion Formulation
3.1.1. Effects of Surfactant HLB Value and Single-Tail Co-Surfactant System
3.1.2. Effect of Co-Solvents
3.1.3. Effect of Co-Surfactant Hydrocarbon Tails
3.1.4. Design of Experiment Program (DoE) with Design Expert® for Low Surfactant Micro- or Nanoemulsions
3.2. Stability Tests of Colloidal Dispersion from DoE
3.3. Skin Permeation of Tripeptide-3 Micro- and Nano-Formulations
3.4. Clinical Evaluation
3.4.1. Skin Irritation Test in Volunteers
3.4.2. Efficacy Evaluation of the Tripeptide-3 NE Product in Volunteers
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Factors | Level | ||
---|---|---|---|
Low Level | High Level | ||
X 1 | HLB value | 11 | 13 |
X 2 | Propylene glycol content | 20% | 40% |
X 3 | Oil content | 5% | 10% |
HLB | Surfactant Mixing Ratio (% w/w) | ME Area (%) | |
---|---|---|---|
Cremophor® RH40 | Span® 80 | ||
7 | 25.2 | 74.8 | 0 |
9 | 43.9 | 56.1 | 0 |
11 | 62.6 | 37.4 | 7.56 |
13 | 81.3 | 18.7 | 9.42 |
HLB | Cremophor® RH40 | Span® 20 | |
7 | N/A | N/A | N/A 1 |
9 | 6.3 | 93.8 | 0 |
11 | 37.5 | 62.5 | 8.61 |
13 | 68.8 | 31.3 | 13.12 |
Electrical Conductivity (μS/cm) | |||
---|---|---|---|
Optimized NE | O/W ME | Bicontinuous ME | W/O ME |
3663.58 ± 5.8 | 208.53 ± 0.7 | 81.92 ± 0.1 | 28.40 ± 0.1 |
Factor 1 | Factor 2 | Factor 3 | Response 1 | Residuals of Response 1 | Response 2 | Residuals of Response 2 | ||
---|---|---|---|---|---|---|---|---|
Std | Run (F) | A:HLB Value | B:PG Content (%) | C:Oil Content (%) | Particle Size (nm) | Turbidity (% Transmittance) | ||
7 | 1 | 11 | 40 | 10 | 901.9 ± 911.20 | −353.35 | 0.0 ± 0.01 | 0.000 |
5 | 2 | 11 | 20 | 10 | 1608.6 ± 1040.90 | 353.35 | 0.0 ± 0.01 | 0.000 |
3 | 3 | 11 | 40 | 5 | 81.2 ± 11.50 | −12.55 | 51.2 ± 0.01 | 5.310 |
2 | 4 | 13 | 20 | 5 | 25.7 ± 1.20 | −1.3 | 70.6 ± 0.58 | −5.565 |
4 | 5 | 13 | 40 | 5 | 28.3 ± 1.80 | 1.3 | 87.3 ± 0.01 | 0.565 |
8 | 6 | 13 | 40 | 10 | 1290.6 ± 1098.20 | 201.1 | 0.0 ± 0.00 | −0.003 |
6 | 7 | 13 | 40 | 10 | 106.3 ± 3.90 | 12.55 | 0.0 ± 0.00 | −5.310 |
1 | 8 | 11 | 20 | 5 | 888.4 ± 809.10 | −201.1 | 0.1 ± 0.01 | 0.003 |
Formulation | Particle Size (nm) Day 0 | Percent Transmittance (%) | Centrifuge at 10,000 rpm 15 min | Heating/Cooling 6 Cycles | Particle Size (nm) After H/C |
---|---|---|---|---|---|
3 | 81.2 ± 11.50 | 51.2 ± 0.01 | Stable | x | N/A |
4 | 25.7 ± 1.20 | 70.6 ± 0.58 | Stable | Stable | 22.5 ± 1.80 |
5 | 28.3 ± 1.80 | 87.3 ± 0.01 | Stable | Stable | 23.58 ± 1.04 * |
Formulation 4 | Particle Size Measurement | |||
---|---|---|---|---|
Day 0 Size nm (PDI) | After 6 H/C Cycles Size nm (PDI) | After 3 F/T Cycles Size nm (PDI) | Day 180 Size nm (PDI) | |
pH 4.5 | 28.1 ± 0.7 (0.27 ± 0.010) | 26.7± 0.3 * (0.149 ± 0.028) * p = 0.0334 | 31.5 ± 0.3 ** (0.262 ± 0.014) ** p = 0.0015 | 29.1± 0.4 (0.075 ± 0.038) p = 0.0599 ns |
pH 5.0 | 23.9 ± 0.3 ### (0.152 ± 0.002) ### p = 0.0007 vs. pH 4.5) | 30.1 ± 0.0 **** (0.258 ± 0.016) **** p < 0.0001 vs. day 0 | 26.1 ± 0.2 *** (0.154 ± 0.01) *** p = 0.0005 vs. day 0 | N/A |
pH 6.0 | 24.3 ± 0.1 ### (0.267 ± 0.032) ### p = 0.0007 vs. pH 4.5 | 25.4± 0.5 * (0.220 ± 0.037) * p = 0.0202 vs. day 0 | 28.0 ± 0.3 *** (0.278 ± 0.015) **** p = 0.0001 vs. day 0 | N/A |
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Magrode, N.; Poomanee, W.; Kiattisin, K.; Ampasavate, C. Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin. Pharmaceutics 2024, 16, 554. https://doi.org/10.3390/pharmaceutics16040554
Magrode N, Poomanee W, Kiattisin K, Ampasavate C. Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin. Pharmaceutics. 2024; 16(4):554. https://doi.org/10.3390/pharmaceutics16040554
Chicago/Turabian StyleMagrode, Nontachai, Worrapan Poomanee, Kanokwan Kiattisin, and Chadarat Ampasavate. 2024. "Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin" Pharmaceutics 16, no. 4: 554. https://doi.org/10.3390/pharmaceutics16040554
APA StyleMagrode, N., Poomanee, W., Kiattisin, K., & Ampasavate, C. (2024). Microemulsions and Nanoemulsions for Topical Delivery of Tripeptide-3: From Design of Experiment to Anti-Sebum Efficacy on Facial Skin. Pharmaceutics, 16(4), 554. https://doi.org/10.3390/pharmaceutics16040554