Transdermal Drug Delivery in the Pig Skin
Abstract
:1. Introduction
2. Materials and Methods
2.1. Substances
2.2. Animal Model and Experimental Procedure
2.3. Microporation
2.4. Electroporation-Iontophoresis
2.5. Intradermal Injection
2.6. High-Pressure Liquid Chromatography (HPLC)
2.7. Histological Assesment
2.8. Indirect Immunohistochemistry
2.9. Quantitative Analysis of the Skin
3. Results
3.1. Histological Findings
3.2. Epidermal Dendritic Cells
3.3. Morphometrical Analysis
3.4. High-Pressure Liquid Chromatography (HPLC)
4. Discussion
5. 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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Active Ingredient | Methocel E4M | Kathon CG | Water P.CSP 100 | Sodium Benzoate | pH |
---|---|---|---|---|---|
Clorhydrate procaine 2% | 1.60% | 0.10% | 96.30% | 5.4 (5.1–5.8) | |
Ketoprofen 5% | 1.60% | 0.10% | 93.30% | 6.6 (6.2–7.0) | |
Biotin 0.5% | 1.60% | 0.10% | 97.80% | 6.7 (6.3–7.1) | |
Anhydrous caffeine 3% | 1.60% | 0.10% | 92.30% | 3% | 7.4 (7.1–7.7) |
Procaine | Ketoprofen | Biotin | Caffeine | |
---|---|---|---|---|
Active ingredient | 50 µL | 50 µL | 50 µL | 50 µL |
Water | 950 µL | 950 µL | 425 µL | |
2.5 pH CH2O2 water | 950 µL | |||
33% Ammonia | 20 µL | 20 µL | ||
Methanol | 425 µL | |||
Dichloromethane | 300 µL | 300 µL | 300 µL | |
Posterior dilution | 1:1 | 1:10 | 1:10 | 1:20 |
Calibration parameters | 5–1000 ng/mL | 5–5000 ng/mL | 5–2000 ng/mL | 1–1000 ng/mL |
Melanocyte Density | Langerhans Cell Density | |||||||
---|---|---|---|---|---|---|---|---|
MN | MN + EP | EP | ID | MN | MN + EP | EP | ID | |
3.3 (2.52–4.08) | 5.1 (4.56–5.64) | 4.2 (3.33–5.07) | 4 (3.23–4.77) | T60 | 1.2 (0.33–2.07) | 2.1 (1.16–0.94) | 1.3 (0.66–1.94) | 1.1 (0.4–1.8) |
4.3 (3.84–4.76) | 8.4 (7.48–9.32) | 11.3 (9.88–12.72) | 3.1 (2.4–3.8) | D7 | 2.2 (1.8–2.6) | 5.3 (4.11–6.49) | 6.8 (5.93–7.67) | 1.7 (0.92–2.48) |
4.6 (4.11–5.09) | 8.1 (6.48–9.72) | 9.4 (8.38–10.42) | 5.2 (4.6–5.8) | D14 | 1.4 (0.74–2.06) | 6.4 (5.29–7.51) | 4.1 (3.27–4.93) | 2.2 (1.45–2.95) |
Variation in Melanocyte Density (T0–D7) | Variation in Langerhans Cell Density (T0–D7) | ||||||
---|---|---|---|---|---|---|---|
MN | MN + EP | EP | ID | MN | MN + EP | EP | ID |
+30.30% | +64.71% | +169.05% | −22.5% | +83.33% | +152.38% | +423.08% | +54.54%% |
Variation in Epidermal Thickness (T0–D14) | Variation in Dermal Thickness (T0–D14) | ||||
---|---|---|---|---|---|
Substance | MN | MN + EP | Substance | MN | MN + EP |
Procaine | −14.72% | −5.96% | Procaine | −7.33% | −5.96% |
Biotin | −20.87% | +18.77% | Biotin | +31.93% | +0.92% |
Caffeine | −30.24% | +39.09% | Caffeine | +12.58% | +4.27% |
Superficial Blood Vessel Density | Fibroblast Density | ||||||||
---|---|---|---|---|---|---|---|---|---|
MN | MN + EP | EP | ID | MN | MN + EP | EP | ID | ||
22.2 (1.42) | 25.3 (3.07) | 21.0 (1.48) | 21.6 (2.8) | Procaine | T60 | 17.3 (1.42) | 14.7 (2) | 17.1 (2.02) | 17.2 (2.18) |
21.1 (2.34) | 41.2 (4.69) | 22.4 (2.5) | 24.0 (1.95) | Procaine | D7 | 16.6 (1.43) | 16.1 (1.42) | 14.3 (1.9) | 16.2 (2.23) |
18.9 (2.21) | 24.3 (2.87) | 24.1 (1.45) | 23.2 (1.4) | Procaine | D14 | 17.3 (1.85) | 18.0 (1.9) | 14.9 (1.81) | 15.3 (1.55) |
22.1 (20.53–23.57) | 26.2 (23.9–28.5) | 19.3 (17.45–21.15) | 21.1 (19.52–22.68) | Ketoprofen | T60 | 15.5 (14.0–17.0) | 17.4 (15.6–19.2) | 13.7 (12.02–15.38) | 17.2 (14.38–20.02) |
19.6 (18.1–21.1) | 36.3 (32.81–39.79) | 18.3 (17.19–19.41) | 20.6 (19.98–22.22) | Ketoprofen | D7 | 18.4 (17.29–19.51) | 14.9 (13.2–16.6) | 16.8 (15.33–18.27) | 20.1 (17.63–22.57) |
18.4 (16.66–20.14) | 25.2 (23.16–27.24) | 4.1 (-3.61–11.81) | 2.2 (-1.48–5.88) | Ketoprofen | D14 | 14.6 (12.75–16.45) | 17.3 (15.06–19.54) | 18.2 (17.03–19.37) | 14.7 (12.6–16.8) |
20.3 (18.51–22.09) | 22.7 (20.91–24.49) | 22.8 (20.57–25.03) | 18.2 (16.95–19.45) | Biotin | T60 | 18.6 (17.04–20.16) | 16.5 (15.14–17.86) | 14.8 (13.2–16.4) | 16.2 (14.48–17.92) |
24.5 (23.14–25.86) | 41.2 (37.44–44.96) | 17.3 (15.87–18.73) | 22.9 (21.53–24.27) | Biotin | D7 | 14.3 (12.62–15.98) | 16.2 (14.2–18.2) | 18.1 (16.8–19.4) | 16.6 (14.91–18.29) |
18.4 (16.95–19.85) | 26.4 (23.98–28.82) | 24.1 (22.29–25.91) | 23.2 (21.42–24.98) | Biotin | D14 | 16.1 (14.31–17.89) | 16.2 (14.3–18.1) | 14.9 (13.45–16.35) | 15.2 (13.48–16.92) |
21.7 (3.32) | 24.6 (3.35) | 20.9 (1.81) | 17.9 (1.58) | Caffeine | T60 | 17.7 (1.95) | 20.1 (2.62) | 16.3 (1.94) | 15.8 (1.66) |
23.2 (2.3) | 39.8 (3.19) | 24.5 (3.04) | 23.2 (1.6) | Caffeine | D7 | 17.2 (1.66) | 15.4 (1.62) | 16.2 (1.47) | 15.9 (1.81) |
21.5 (3.23) | 26.1 (2.88) | 26.3 (1.6) | 27.1 (2.66) | Caffeine | D14 | 16.1 (1.73) | 18.3 (1.49) | 15.8 (1.14) | 18.4 (1.28) |
Variation in Superficial Blood Vessel Density (T0–D7) | Variation in Fibroblast Density (T0–D7) | |||||||
---|---|---|---|---|---|---|---|---|
Substance | MN | MN + EP | EP | ID | MN | MN + EP | EP | ID |
Procaine | −4.95% | +62.85% | +6.67% | +11.11% | −4.46% | +9.52% | −16.37% | −5.81% |
Ketoprofen | −11.31 | +38.55% | −5.18% | −2.24% | +18.71% | −14.37% | +22.63% | +16.86% |
Biotin | +20.69% | +81.50% | −22.30% | +25.82% | −23.18% | −1.81% | +22.23% | +2.47% |
Caffeine | +6.91% | +61.79% | +17.22% | +29.61% | −2.82% | −23.38% | −0.61% | +0.63% |
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Ordiz, I.; Vega, J.A.; Martín-Sanz, R.; García-Suárez, O.; del Valle, M.E.; Feito, J. Transdermal Drug Delivery in the Pig Skin. Pharmaceutics 2021, 13, 2016. https://doi.org/10.3390/pharmaceutics13122016
Ordiz I, Vega JA, Martín-Sanz R, García-Suárez O, del Valle ME, Feito J. Transdermal Drug Delivery in the Pig Skin. Pharmaceutics. 2021; 13(12):2016. https://doi.org/10.3390/pharmaceutics13122016
Chicago/Turabian StyleOrdiz, Ignacio, José A. Vega, Raquel Martín-Sanz, Olivia García-Suárez, Miguel E. del Valle, and Jorge Feito. 2021. "Transdermal Drug Delivery in the Pig Skin" Pharmaceutics 13, no. 12: 2016. https://doi.org/10.3390/pharmaceutics13122016