Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Experimental Design
2.3. Preparation of CLEP Formulations
2.4. Characterization of ILEP Formulations
2.4.1. Entrapment Efficiency Measurement
2.4.2. Vesicle Size Measurement
2.5. Optimization of ILEP Formulations
2.6. Characterization of the Optimized ILEP Formulation
2.6.1. Differential Scanning Calorimetry (DSC)
2.6.2. Transmission Electron Microscopy (TEM)
2.6.3. Zeta Potential and Size Distribution
2.6.4. In Vitro Release Study
2.6.5. Ex Vivo Permeation Study
2.7. In Vivo Evaluation of Optimized ILEP Formulation
2.7.1. Animals
2.7.2. Treatment Protocol
2.7.3. Neurobehavioral Study
2.7.4. Histopathology Study
2.7.5. Toxicity Studies
2.8. Statistical Analysis
3. Results
3.1. Experimental Design
3.2. Characterization of ILEP Formulations
3.3. Optimization of ILEP Formulation
3.4. Characterization of Optimized ILEP Formulation
3.4.1. DSC
3.4.2. TEM
3.4.3. Zeta Potential and Size Distribution
3.4.4. In Vitro Release Study
3.4.5. Ex Vivo Skin Permeation Study
3.5. In Vivo Evaluation of Optimized ILEP Formulation
3.5.1. Anti-Stroke Activity Measurement
3.5.2. Toxicity Studies
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Independent Variables | Coded Values | |||||||
---|---|---|---|---|---|---|---|---|
−1 | 0 | +1 | ||||||
X1: concentration of propylene glycol (%) | 5 | 10 | 15 | |||||
X2: concentration of phospholipid (%) | 1 | 3 | 5 | |||||
X3: concentration of ethanol (%) | 0 | 5 | 10 | |||||
Dependent Variables | Model | Lack of Fit | F-value | p-value | Constraints | |||
Y1: Entrapment efficiency (%) | Quadratic | 0.8584 | 3499.20 | <0.0001 | Maximize | |||
Y2: Vesicle size (nm) | Quadratic | 0.4792 | 1337.81 | <0.0001 | Minimize |
Run | Factors Levels in Actual Values | Responses (n = 3) | |||
---|---|---|---|---|---|
X1: Concentration of Propylene Glycol (%) | X2: Concentration of Phospholipid (%) | X3: Concentration of Ethanol (%) | Entrapment Efficiency (% ± SD) | Vesicle Size (nm ± SD) | |
F1 | 10 | 1 | 10 | 78.84 ± 0.22 | 141.77 ± 4.90 |
F2 | 10 | 1 | 0 | 74.30 ± 0.30 | 195.53 ± 4.80 |
F3 | 10 | 3 | 5 | 84.27 ± 0.25 | 217.33 ± 3.79 |
F4 | 5 | 3 | 10 | 85.66 ± 0.24 | 203.00 ± 3.61 |
F5 | 5 | 3 | 0 | 81.32 ± 0.25 | 261.33 ± 5.51 |
F6 | 15 | 3 | 0 | 82.90 ± 0.19 | 230.60 ± 3.67 |
F7 | 5 | 1 | 5 | 75.85 ± 0.26 | 179.83 ± 7.15 |
F8 | 10 | 3 | 5 | 84.33 ± 0.22 | 215.67 ± 7.02 |
F9 | 10 | 5 | 10 | 94.34 ± 0.24 | 369.67 ± 4.51 |
F10 | 15 | 5 | 5 | 93.01 ± 0.21 | 372.13 ± 6.74 |
F11 | 15 | 1 | 5 | 77.30 ± 0.22 | 151.80 ± 9.82 |
F12 | 15 | 3 | 10 | 87.46 ± 0.27 | 170.47 ± 3.88 |
F13 | 10 | 5 | 0 | 90.00 ± 0.19 | 424.57 ± 5.52 |
F14 | 5 | 5 | 5 | 91.40 ± 0.27 | 405.67 ± 7.02 |
F15 | 10 | 3 | 5 | 84.31 ± 0.24 | 213.33 ± 4.51 |
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Abou-Taleb, H.A.; Aldosari, B.N.; Zaki, R.M.; Afzal, O.; Tulbah, A.S.; Shahataa, M.G.; Abo El-Ela, F.I.; Salem, H.F.; Fouad, A.G. Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke. Pharmaceutics 2023, 15, 2242. https://doi.org/10.3390/pharmaceutics15092242
Abou-Taleb HA, Aldosari BN, Zaki RM, Afzal O, Tulbah AS, Shahataa MG, Abo El-Ela FI, Salem HF, Fouad AG. Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke. Pharmaceutics. 2023; 15(9):2242. https://doi.org/10.3390/pharmaceutics15092242
Chicago/Turabian StyleAbou-Taleb, Heba A., Basmah Nasser Aldosari, Randa Mohammed Zaki, Obaid Afzal, Alaa S. Tulbah, Mary Girgis Shahataa, Fatma I. Abo El-Ela, Heba F. Salem, and Amr Gamal Fouad. 2023. "Formulation and Therapeutic Evaluation of Isoxsuprine-Loaded Nanoparticles against Diabetes-Associated Stroke" Pharmaceutics 15, no. 9: 2242. https://doi.org/10.3390/pharmaceutics15092242