Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Capsaicin Contents in Chili Extract
2.3. HPLC Analysis
2.4. Pre-Formulation for Capsaicin-Loaded Lipid-Based Nanoparticles
2.4.1. Lipid Selection for SLN and NLC
2.4.2. Preparation of SLN and NLC
2.4.3. Preparation of Chili Extract-Loaded Lipid Nanoparticle Incorporated in Hydrogel
2.5. Characterizing the Chili Extract-Loaded Nanodelivery System
2.5.1. Particle Size, Size Distribution and Zeta Potential Analysis
2.5.2. Determining Entrapment Efficiency (EE) and Loading Capacity (LC)
2.5.3. Transmission Electron Microscopy Analysis
2.5.4. Differential Scanning Calorimetry (DSC) Analysis
2.6. In Vitro Release Kinetics Study
2.7. In Vitro Skin Permeation Study
2.7.1. Drug Permeation
2.7.2. Skin Distribution
2.8. Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) Assay
2.9. In Vitro Skin Irritation Test Using a Three-Dimensional EpiDerm Skin Model
2.9.1. MTT Assay on the 3D EpiDermTM Skin Model
2.9.2. ELISA Assay
2.10. Statistical Analysis
3. Results and Discussion
3.1. Capsaicin Contents in Chili Extract
3.2. Pre-Formulation for Capsaicin Loaded Lipid-Based Nanoparticles
3.2.1. Lipid Selection for SLN and NLC
3.2.2. Characterizing the Chili Extract-Loaded Nanodelivery System
3.2.3. Entrapment Efficiency (EE) and Loading Capacity (LC)
3.2.4. TEM Investigation
3.2.5. Differential Scanning Calorimetry (DSC) Analysis
3.3. In Vitro Release Kinetics Study
3.4. In Vitro Skin Permeation Study
3.5. Irritation Properties of Chili Extract Determined by the HET-CAM Assay
3.6. In Vitro Skin Irritation Test Using the EpiDermTM Model
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Formulations | Lipid Phase | Particle Size (nm) | PDI | Zeta Potential (mV) |
---|---|---|---|---|
SLN 1:4 * | GBH + COH | 153.74 ± 6.72 | 0.39 ± 0.01 | −44.26 ± 1.22 |
GBH + COH + chili | 176.80 ± 6.19 | 0.15 ± 0.07 | −33.64 ± 1.09 | |
GMS + COH | 129.42 ± 5.80 | 0.33 ± 0.05 | −42.16 ± 0.77 | |
GMS + COH + chili | 148.42 ± 4.80 | 0.22 ± 0.04 | −40.78 ± 0.68 | |
GBH + SOH | 154.68 ± 11.87 | 0.46 ± 0.01 | −33.14 ± 1.31 | |
GBH + SOH + chili | 154.66 ± 4.22 | 0.17 ± 0.02 | −26.60 ± 1.84 | |
GMS + SOH | 113.74 ± 3.58 | 0.43 ± 0.06 | −34.94 ± 1.39 | |
GMS + SOH + chili | 160.86 ± 5.47 | 0.19 ± 0.04 | −28.24 ± 0.69 | |
NLC 1 4 * | GBH + COH + IPM | 150.98 ± 3.09 | 0.31 ± 0.02 | −35.40 ± 1.10 |
GBH + COH + IPM + chili | 156.10 ± 2.82 | 0.11 ± 0.02 | −31.40 ± 1.45 | |
GMS + COH + IPM | 139.34 ± 3.95 | 0.38 ± 0.03 | −34.64 ± 1.37 | |
GMS + COH + IPM + chili | 148.50 ± 2.94 | 0.12 ± 0.03 | −29.58 ± 1.37 | |
GBH + SOH + IPM | 150.42 ± 4.12 | 0.43 ±0.03 | −31.54 ± 1.96 | |
GBH + SOH + IPM + chili | 154.86 ± 1.66 | 0.16 ± 0.05 | −30.90 ± 0.94 | |
GMS + SOH + IPM | 126.84 ± 4.61 | 0.38 ± 0.06 | −30.92 ± 0.95 | |
GMS + SOH + IPM + chili | 150.08 ± 2.16 | 0.16 ± 0.03 | −27.10 ± 0.91 |
Methods | Formulations | Particle Size (nm) | PDI | Zeta Potential (mV) |
---|---|---|---|---|
Probe sonication | SLN | 1671.00 ± 643.07 | 0.97 ± 0.07 | −45.18 ± 1.34 |
NLC | 502.24 ± 136.29 | 0.68 ± 0.08 | −45.80 ± 0.83 | |
High pressure homogenizer | SLN | 129.42 ± 5.80 | 0.33 ± 0.05 | −42.16 ± 0.77 |
NLC | 139.34 ± 3.95 | 0.38 ± 0.03 | −34.64 ± 1.37 |
Capsaicin Conc. (%) | Formulation | Lipid Phase (Wax) | % EE | % LC |
---|---|---|---|---|
0.075 | SLN | GBH + COH + chili | 78.33 ± 0.25 | 2.35 ± 0.01 |
GMS + COH + chili | 82.23 ± 1.69 | 2.47 ± 0.05 | ||
GBH + SOH + chili | 77.27 ± 5.98 | 2.32 ± 0.18 | ||
GMS + SOH + chili | 76.49 ± 8.85 | 2.29 ± 0.27 | ||
NLC | GBH + COH + IPM + chili | 85.99 ± 6.37 | 2.58 ± 0.19 | |
GMS + COH + IPM + chili | 91.67 ± 4.02 | 2.75 ± 0.12 | ||
GBH + SOH + IPM + chili | 84.65 ± 3.01 | 2.54 ± 0.09 | ||
GMS + SOH + IPM + chili | 85.43 ± 1.29 | 2.56 ± 0.04 | ||
0.25 | SLN | GMS + COH + chili | 68.63 ± 0.54 | 6.86 ± 0.05 |
NLC | GMS + COH + IPM + chili | 85.27 ± 0.12 | 8.53 ± 0.01 |
Samples | Onset (°C) | Peak (°C) | Endset (°C) | Integral (mJ) | ΔH (J/g) | % Crystallinity |
---|---|---|---|---|---|---|
GMS | 57.81 | 66.77 | 70.83 | −1043.38 | −163.03 | - |
COH | 48.06 | 51.35 | 55.69 | −1291.74 | −205.04 | - |
Physical mixture | 49.61 | 52.15 | 56.11 | −719.92 | −110.76 | 100.00 |
SLN blank | 34.75 | 37.88 | 40.97 | −123.57 | −14.54 | 65.64 |
NLC blank | 34.88 | 38.72 | 42.81 | −52.26 | −6.15 | 39.66 |
SLN chili | 30.91 | 39.84 | 45.24 | −61.72 | −7.09 | 15.33 |
NLC chili | 30.49 | 35.21 | 44.19 | −10.81 | −1.26 | 3.13 |
Formulation | Flux (µg/cm2 h) | Lag Time (h) | Permeability Coefficient (cm/h) × 10−5 | Q24h (µg) | Enhancement Ratio (Er) |
---|---|---|---|---|---|
Chili extract | 0.28 ± 0.05 | 5.95 ± 0.15 | 11.36 ± 1.90 | 9.05 ± 1.54 | 1.00 ± 0.00 |
SLN chili | 0.37 ± 0.12 | 2.31 ± 0.07 * | 17.17 ± 3.31 * | 11.54 ± 1.78 | 1.39 ± 0.12 |
NLC chili | 0.45 ± 0.16 | 2.30 ± 0.06 * | 21.02 ± 4.38 * | 13.68 ± 1.79 * | 1.70 ± 0.17 |
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Anantaworasakul, P.; Chaiyana, W.; Michniak-Kohn, B.B.; Rungseevijitprapa, W.; Ampasavate, C. Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation. Pharmaceutics 2020, 12, 463. https://doi.org/10.3390/pharmaceutics12050463
Anantaworasakul P, Chaiyana W, Michniak-Kohn BB, Rungseevijitprapa W, Ampasavate C. Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation. Pharmaceutics. 2020; 12(5):463. https://doi.org/10.3390/pharmaceutics12050463
Chicago/Turabian StyleAnantaworasakul, Phunsuk, Wantida Chaiyana, Bozena B. Michniak-Kohn, Wandee Rungseevijitprapa, and Chadarat Ampasavate. 2020. "Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation" Pharmaceutics 12, no. 5: 463. https://doi.org/10.3390/pharmaceutics12050463
APA StyleAnantaworasakul, P., Chaiyana, W., Michniak-Kohn, B. B., Rungseevijitprapa, W., & Ampasavate, C. (2020). Enhanced Transdermal Delivery of Concentrated Capsaicin from Chili Extract-Loaded Lipid Nanoparticles with Reduced Skin Irritation. Pharmaceutics, 12(5), 463. https://doi.org/10.3390/pharmaceutics12050463