Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methods
2.2.1. Nanoemulsion Preparation
2.2.2. Droplet Size and Size Distribution Analysis
2.2.3. Determination of the Surface Charge of the Nanodroplets
2.2.4. pH Measurements
2.2.5. In Vitro Safety Assessment of the Nanoemulsions—Cytotoxicity Assay
Cell Line
Determination of the Cell Survival
2.2.6. In Vivo Assessment of the Irritation Potential of the Blank Nanoemulsions
- nanoemulsion without chemical penetration enhancers (F1);
- nanoemulsion with pinene as a chemical penetration enhancer (F1_PIN);
- nanoemulsion with eucalyptol as a chemical penetration enhancer (F1_EUC).
- trans-epidermal water loss (TEWL);
- erythema index (EI);
- degree of hydration of the stratum corneum (stratum corneum hydration—SCH).
2.2.7. In Vivo Penetration Study of Curcumin from Developed Curcumin-Loaded Nanoemulsions
- formulation with pinene (F1_PIN_CU);
- formulation with eucalyptol (F1_EUC_CU);
- formulation without monoterpenes (F1_CU).
2.2.8. Iontophoresis
Irritation Potential Assessment of the Proposed Iontophoresis Protocols
- continuous flow for 15 min (15-0);
- 3 min of continuous flow and 2 min pause (3-2; 5 cycles);
- 5 min of continuous flow and 1 min pause (5-1; 3 cycles).
In Vivo Penetration Study of Curcumin after the Application of Iontophoresis
2.2.9. LC-MS/MS Analysis
2.2.10. Statistical Analysis
3. Results and Discussion
3.1. In Vitro Characterization of the Selected Nanoemulsions
3.2. In Vivo Safety Study of the Blank Nanoemulsions
3.3. Selection of Experimental Conditions for the Iontophoresis: An In Vivo Safety Study
- continuous current flow for 15 min—15-0;
- discontinuous flow—5 min of flow with 1 min break (3 cycles)—5-1;
- discontinuous flow—3 min flow with 2 min break (5 cycles)—3-2.
3.4. In Vivo Assessment of Curcumin Penetration through the Superficial Skin Layers after the Application of Curcumin-Loaded Nanoemulsions: Comparison of the Effect of Chemical Penetration Enhancers and Iontophoresis
- electromigration;
- electroosmosis;
- passive diffusion.
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Formulation | MCT | Eucalyptol | Pinene | Curcumin | Soybean Lecithin | Polysorbate 80 | Water |
---|---|---|---|---|---|---|---|
F1 | 10 | / | / | / | 1 | 9 | 80 |
F1_EUC | 5 | 5 | / | ||||
F1_PIN | 5 | / | 5 | ||||
F1_CU | 10 | / | / | 0.3 | 79.7 | ||
F1_EUC_CU | 5 | 5 | / | ||||
F1_PIN_CU | 5 | / | 5 |
Formulation | pH | Zeta Potential (mV) |
---|---|---|
F1 | 4.78 ± 0.04 | −33.07 ± 0.95 |
F1_EUC | 6.25 ± 0.03 | −21.17 ± 1.17 |
F1_PIN | 4.65 ± 0.01 | −39.50 ± 1.30 |
F1_CU | 5.36 ± 0.03 | −30.33 ± 1.81 |
F1_EUC_CU | 6.23 ± 0.01 | −31.10 ± 0.10 |
F1_PIN_CU | 5.80 ± 0.03 | −22.27 ± 0.06 |
Formulation | Cumulative Amount of Curcumin That Penetrated through the Stratum Corneum per Unit Area (μg/cm2) |
---|---|
F1_CU | 30.62 ± 2.62 |
F1_EUC_CU | 34.24 ± 5.68 # |
F1_PIN_CU | 21.61 ± 4.01 * |
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Nikolić, I.; Simić, M.; Pantelić, I.; Stojanović, G.; Antić Stanković, J.; Marković, B.; Savić, S. Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis. Pharmaceutics 2022, 14, 1144. https://doi.org/10.3390/pharmaceutics14061144
Nikolić I, Simić M, Pantelić I, Stojanović G, Antić Stanković J, Marković B, Savić S. Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis. Pharmaceutics. 2022; 14(6):1144. https://doi.org/10.3390/pharmaceutics14061144
Chicago/Turabian StyleNikolić, Ines, Mitar Simić, Ivana Pantelić, Goran Stojanović, Jelena Antić Stanković, Bojan Marković, and Snežana Savić. 2022. "Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis" Pharmaceutics 14, no. 6: 1144. https://doi.org/10.3390/pharmaceutics14061144
APA StyleNikolić, I., Simić, M., Pantelić, I., Stojanović, G., Antić Stanković, J., Marković, B., & Savić, S. (2022). Chemical vs. Physical Methods to Improve Dermal Drug Delivery: A Case Study with Nanoemulsions and Iontophoresis. Pharmaceutics, 14(6), 1144. https://doi.org/10.3390/pharmaceutics14061144