Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization
2.2. Effect on Particle Size (Y1)
2.2.1. Impact of PLGA
2.2.2. Impact of PVA
2.2.3. Impact of Sonication Time (ST)
2.3. Effect on PDI (Y2)
2.3.1. Impact of PLGA
2.3.2. Impact of PVA
2.3.3. Impact of ST
2.4. Y3: Effect of on EE
2.4.1. Impact of PLGA
2.4.2. Impact of PVA
2.4.3. Impact of ST
2.5. Numerical Optimization
2.6. Characterization of α-MNG-PLGA NPs
2.6.1. Differential Scanning Calorimetry of α-MNG NPs
2.6.2. FT-IR Spectral Analysis of α-MNG NPs
2.7. Drug Release and Kinetic Study
2.8. Gel Characteristics
2.9. Ex Vivo Skin Permeation
Drug Estimation across Skin Layer
2.10. Confocal Laser Microscopy
2.11. Cell Viability Assay
2.12. In Vitro Antioxidant Activity
2.13. Stability Studies
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Fabrication of α-Mangostin-Loaded PLGA Nanoparticle
4.3. Analytical Method
4.4. Formulation Optimization
4.5. Nanoparticle Characterization
4.5.1. Particle Sizes and Their Distribution
4.5.2. Drug Entrapment and Loading
4.5.3. Transmission Electron Microscopy
4.5.4. Infrared Spectroscopy
4.5.5. Differential Scanning Calorimetry
4.5.6. Drug Release and Kinetics Studies
4.5.7. Preparation of Gel
Gel Characterization
4.5.8. Ex Vivo Skin Permeation Studies
4.5.9. Drug Concentration Estimation in Skin Strata
4.5.10. Confocal Microscopy
4.5.11. Cell Viability Study
4.5.12. Free Radical Scavenging Activity
4.5.13. Stability Study
4.5.14. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Independent Variables | Level Used (Coded) | ||
---|---|---|---|
Low (−1) | Medium (0) | High (+1) | |
X1: Polymer concentration (% w/v) | 2.5 | 3.00 | 3.50 |
X2: Surfactant concentration (% w/v) | 1.00 | 1.75 | 2.50 |
X3: Sonication time (min) | 4 | 8 | 12 |
Dependent variables | |||
Y1: Particle size (nm) | Minimize | ||
Y2: PDI | Minimize | ||
Y3: Entrapment efficiency (%) | Maximize |
Formulation Code | Independent Variables | Responses | ||||
---|---|---|---|---|---|---|
X1 (% w/v) | X2 (% w/v) | X3 (min) | Y1 (nm) | Y2 | Y3 (%) | |
* NP1 | 3.00 | 1.75 | 8.00 | 176 ± 19.04 | 0.205 ± 0.02 | 78 ± 8.67 |
NP2 | 2.50 | 1.00 | 8.00 | 187 ± 24.12 | 0.302 ± 0.03 | 68 ± 6.12 |
* NP3 | 3.00 | 1.75 | 8.00 | 171 ± 15.67 | 0.210 ± 0.04 | 79 ± 9.34 |
NP4 | 3.50 | 1.75 | 12.00 | 167 ± 13.45 | 0.233 ± 0.02 | 83 ± 7.98 |
* NP5 | 3.00 | 1.75 | 8.00 | 172 ± 21.81 | 0.206 ± 0.01 | 74.9 ± 6.80 |
NP6 | 3.00 | 2.50 | 12.00 | 125 ± 10.01 | 0.276 ± 0.05 | 75 ± 10.07 |
NP7 | 2.50 | 1.75 | 4.00 | 230 ± 33.76 | 0.281 ± 0.01 | 51 ± 9.23 |
NP8 | 3.50 | 1.00 | 8.00 | 172 ± 11.93 | 0.215 ± 0.03 | 83 ± 9.65 |
NP9 | 3.00 | 2.50 | 4.00 | 198 ± 19.62 | 0.306 ±0.04 | 72 ± 11.92 |
NP10 | 2.50 | 2.50 | 8.00 | 167 ± 17.12 | 0.321 ± 0.02 | 53 ± 4.47 |
* NP11 | 3.00 | 1.75 | 8.00 | 173 ± 16.02 | 0.199 ± 0.01 | 76 ± 11.21 |
NP12 | 3.50 | 2.50 | 8.00 | 162 ± 14.03 | 0.268 ± 0.02 | 90 ± 12.76 |
NP13 | 3.00 | 1.00 | 4.00 | 194 ± 24.98 | 0.203 ± 0.07 | 74 ± 9.67 |
NP14 | 3.50 | 1.75 | 4.00 | 174 ± 17.54 | 0.222 ± 0.09 | 81 ± 8.78 |
NP15 | 3.00 | 1.00 | 12.00 | 166 ± 19.32 | 0.312 ± 0.06 | 84 ± 7.43 |
* NP16 | 3.00 | 1.75 | 8.00 | 172 ± 21.78 | 0.212 ± 0.03 | 77 ± 9.56 |
NP17 | 2.50 | 1.75 | 12.00 | 132 ± 12.67 | 0.321 ± 0.05 | 61 ± 7.12 |
Response Surface Quadratic Model | R-Squared | Adj R-Squared | Pred R-Squared | Adeq Precision | PRESS | % CV | Mean | SD |
---|---|---|---|---|---|---|---|---|
Response 1 (Y1) | 0.9970 | 0.9940 | 0.9853 | 79.146 | 128.59 | 1.04 | 172.82 | 1.81 |
Response 2 (Y2) | 0.9942 | 0.9867 | 0.9476 | 28.134 | 1.874 × 10−3 | 2.16 | 0.25 | 5.457 × 10−3 |
Response 3 (Y3) | 0.9935 | 0.9852 | 0.9799 | 39.150 | 36.26 | 1.74 | 74.11 | 1.29 |
PS = +173.16 – 5.12 × X1 – 8.37 × X2 – 25.75 × X3 + 2.50 × X1 × X2 + 22.75 × X1 × X3 – 11.25 × X2 × X3 + 2.14 × X12 – 2.86 × X22 | ||||||||
PDI = +0.21 – 0.036 × X1 + 0.017 × X2 + 0.016 × X3 + 8.500E − 0.03 × X1 × X2 – 7.250 – 0.03 × X1 × X3 – 0.035 × X2 × X3 + 0.03 × X12 + 0.040 × X22 + 0.028 × X32 | ||||||||
EE = +76.98 + 13.00 × X1 − 2.37 × X2 + 3.13 × X3 + 5.50 × X1 × X2 − 2.00 × X1 × X3 – 1.75 × X2 × X3 − 5.37 × X12 + 1.88 × X22 − 2.61 × X32 |
Variables | Optimum Composition | Response | Observed Value of Response | Predicted Value of Response | Percentage Error |
---|---|---|---|---|---|
X1 | 3.39 % w/v | Y1 | 168.06 ± 17.02 | 150.87 | 11.39 |
X2 | 1.82 % w/v | Y2 | 0.201 ± 0.01 | 0.214 | −6.07 |
X3 | 8.79 min | Y3 | 84.26 ± 8.23 | 79.16 | 6.44 |
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Md, S.; Alhakamy, N.A.; Neamatallah, T.; Alshehri, S.; Mujtaba, M.A.; Riadi, Y.; Radhakrishnan, A.K.; Khalilullah, H.; Gupta, M.; Akhter, M.H. Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer. Gels 2021, 7, 230. https://doi.org/10.3390/gels7040230
Md S, Alhakamy NA, Neamatallah T, Alshehri S, Mujtaba MA, Riadi Y, Radhakrishnan AK, Khalilullah H, Gupta M, Akhter MH. Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer. Gels. 2021; 7(4):230. https://doi.org/10.3390/gels7040230
Chicago/Turabian StyleMd, Shadab, Nabil A. Alhakamy, Thikryat Neamatallah, Samah Alshehri, Md Ali Mujtaba, Yassine Riadi, Ammu K. Radhakrishnan, Habibullah Khalilullah, Manish Gupta, and Md Habban Akhter. 2021. "Development, Characterization, and Evaluation of α-Mangostin-Loaded Polymeric Nanoparticle Gel for Topical Therapy in Skin Cancer" Gels 7, no. 4: 230. https://doi.org/10.3390/gels7040230