Development of Nanogel Loaded with Lidocaine for Wound-Healing: Illustration of Improved Drug Deposition and Skin Safety Analysis
Abstract
:1. Introduction
2. Results and Discussion
2.1. Selection of Suitable Excipients
2.2. Optimization and Statistical Analysis of Variables
2.2.1. Effect of Independent Variables on Particle Size of Nanoemulsion
2.2.2. Effect of Independent Variables on PDI of Nanoemulsion
2.2.3. Effect of Independent Variables on Percent Transmittance
2.2.4. Selection of Optimized Formulation
2.3. Evaluation of Optimized Nanoemulsion
2.4. Evaluation of Nanogel
2.4.1. In Vitro Drug Release Study
2.4.2. Dermatokinetic Study
2.4.3. In Vivo Skin Safety Study
2.4.4. Stability Studies
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Solubility Studies for the Selection of Suitable Excipients
4.3. Fabrication and Optimization of Lidocaine Nanoemulsion
4.4. Characterization of Optimized Nanoemulsion
4.4.1. Determination of particle Size, PDI and Percent Transmittance
4.4.2. Determination of Thermodynamic Stability
4.4.3. Determination of Refractive Index
4.4.4. Determination of Zeta Potential
4.5. Development of Drug-Loaded Nanogel
4.6. Evaluation of Nanogel
4.6.1. Morphological and pH Determination
4.6.2. Determination of Spreadability and Extrudability
4.6.3. Determination of Drug Content
4.6.4. In Vitro Drug Release Study
4.6.5. Dermatokinetic Study
4.6.6. In Vivo Skin Safety Study
4.6.7. Stability Studies
4.7. Statistical Analysis
5. Patents
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Factors | Level Used | |
---|---|---|
Independent variables | Low | High |
Oil (%w/w) | 2 | 4 |
Emulsifier (%w/w) | 2 | 6 |
Dependent variables | Constraints | |
Particle size (nm) | Minimum | |
PDI | Minimum | |
Transmittance (%) | Maximum |
Run | Factor 1 A: Oil (% w/w) | Factor 2 B: Emulsifier (% w/w) | Response 1 Particle Size (nm) | Response 2 PDI | Response 3 Transmittance (%) | |||
---|---|---|---|---|---|---|---|---|
Actual | Predicted | Actual | Predicted | Actual | Predicted | |||
1 | 3 | 6.82843 | 112 | 112.25 | 0.27 | 0.2646 | 91.16 | 91.12 |
2 | 3 | 1.17157 | 176 | 175.00 | 0.71 | 0.7179 | 80.05 | 81.16 |
3 | 3 | 4 | 141 | 139.80 | 0.35 | 0.3560 | 87.64 | 87.66 |
4 | 3 | 4 | 140 | 139.80 | 0.34 | 0.3560 | 87.82 | 87.66 |
5 | 4 | 2 | 169 | 173.23 | 0.66 | 0.6888 | 83.27 | 81.90 |
6 | 4.41421 | 4 | 161 | 155.79 | 0.58 | 0.5320 | 84.88 | 86.02 |
7 | 2 | 2 | 151 | 148.39 | 0.59 | 0.5492 | 86.98 | 86.47 |
8 | 2 | 6 | 101 | 97.52 | 0.25 | 0.2187 | 93.25 | 93.55 |
9 | 4 | 6 | 132 | 135.36 | 0.34 | 0.3783 | 89.47 | 88.91 |
10 | 3 | 4 | 138 | 139.80 | 0.34 | 0.3560 | 88.18 | 87.66 |
11 | 1.58579 | 4 | 107 | 111.46 | 0.27 | 0.3205 | 92.59 | 92.52 |
12 | 3 | 4 | 139 | 139.80 | 0.36 | 0.3560 | 87.89 | 87.66 |
13 | 3 | 4 | 141 | 139.80 | 0.39 | 0.3560 | 86.77 | 87.66 |
Response | Mean Square | Standard Deviation | R2 | Adjusted R2 | Predicted R2 | Suggested Model |
---|---|---|---|---|---|---|
Particle size (nm) | 1209.97 | 3.84 | 0.9832 | 0.9713 | 0.8870 | Quadratic |
PDI | 0.0574 | 0.0407 | 0.9612 | 0.9334 | 0.7558 | Quadratic |
Parameters | Nanogel | Conventional Gel |
---|---|---|
Colour | Creamy | White |
Appearance | Translucent | Translucent |
Washability | Good washability | Good washability |
Homogeneity | Good | Good |
pH | 6.87 ± 0.51 | 6.93 ± 0.32 |
Spreadability (gm.cm/sec) | 73.32 ± 4.59 | 70.42 ± 4.69 |
Extrudability (gm/cm2) | 107.41 ± 6.42 | 114.81 ± 6.42 |
Drug content (Percent) | 99.94 ± 1.70 | 100.33 ± 2.08 |
Dermatokinetic Parameters | Nanogel | Conventional Gel | ||
---|---|---|---|---|
Epidermis | Dermis | Epidermis | Dermis | |
Cmax (mg/cm2) | 2.64 ± 0.02 | 2.53 ± 0.06 | 1.48 ± 0.02 | 1.46 ± 0.04 |
Tmax (h) | 0.83 ± 0.29 | 1.33 ± 0.58 | 1.33 ± 0.58 | 1.67 ± 0.58 |
AUC0–12 h (mg/cm2h) | 26.15 ± 0.92 | 26.39 ± 0.91 | 14.13 ± 0.49 | 14.40 ± 0.18 |
Ke (h−1) | 0.016 ± 0.004 | 0.010 ± 0.001 | 0.02 ± 0.01 | 0.021 ± 0.004 |
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Ali, A.; Ali, A.; Rahman, M.A.; Warsi, M.H.; Yusuf, M.; Alam, P. Development of Nanogel Loaded with Lidocaine for Wound-Healing: Illustration of Improved Drug Deposition and Skin Safety Analysis. Gels 2022, 8, 466. https://doi.org/10.3390/gels8080466
Ali A, Ali A, Rahman MA, Warsi MH, Yusuf M, Alam P. Development of Nanogel Loaded with Lidocaine for Wound-Healing: Illustration of Improved Drug Deposition and Skin Safety Analysis. Gels. 2022; 8(8):466. https://doi.org/10.3390/gels8080466
Chicago/Turabian StyleAli, Amena, Abuzer Ali, Mohammad Akhlaquer Rahman, Musarrat Husain Warsi, Mohammad Yusuf, and Prawez Alam. 2022. "Development of Nanogel Loaded with Lidocaine for Wound-Healing: Illustration of Improved Drug Deposition and Skin Safety Analysis" Gels 8, no. 8: 466. https://doi.org/10.3390/gels8080466