Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Methodology
2.2.1. Solubility Study of EH in Different Solid Lipids
2.2.2. Experimental Design
2.2.3. Preparation of EH-Loaded Mucoadhesive Emulsomes
2.2.4. Evaluation of EH-Loaded Mucoadhesive Emulsomes
- EE% = EH entrapped amount/EH initial amount × 100
- DLC was determined by the following Equation [24]:
- DCL = (Total entrapped EH-free EH) weight of emulsomes
- The experiment was done in triplicates and results were expressed as mean ± SD
Particle Size Analysis
Zeta Potential Determination
2.2.5. Permeation Study of EH from the Prepared Mucoadhesive Emulsomes through the Nasal Mucosa
Nasal Mucosa Preparation
Apparatus Assembly
Determination of the Residence Time (RT) of the Prepared EH-Loaded Mucoadhesive Emulsomes
2.2.6. Optimization of EH-Loaded Mucoadhesive Emulsomes
2.2.7. Morphological Evaluation
2.2.8. Stability Study of the Optimized Formulation
2.2.9. In-Vivo Biodistribution Studies
Animals
Experimental Protocol
- Group 1: Intranasal (i.n) aqueous solution of EH (equivalent to 1 mg/kg body weight) (10 µL in each nostril).
- Group 2: Intravenous (i.v) aqueous EHsolution (equivalent to 1 mg/kg body weight) that was injected through the lateral tail vein of the mice.
- Group 3: The selected EHformulation at a dose equivalent to 1 mg/kg body weight was instilled into the nose of the mice fixed in a prostrate position.
Biochemical Analysis
2.2.10. Histopathological Examination
2.2.11. Statistical Analysis
3. Results and Discussion
3.1. Solubility Test
3.2. EH-Emulsomes Formulation
3.3. Evaluation of the Prepared Emulsomes
3.3.1. Effect of Different Factors on Dependent Variables
3.3.2. Optimization of EH Mucoadhesive Emulsomes
3.4. Morphological Evaluation
3.5. Stability Study of the Optimized Formulation
3.6. In Vivo Biodistribution Study
3.7. Histopathological Study
4. 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 | Level of Variables Low(−1)–High (1) |
---|---|
X1: PC: CA molar ratio | 1–2 |
X2: EH: T. lipids molar ratio | 0.25–0.5 |
X3: TMC Conc. | 0.25% w/v–0.5% w/v |
Responses | Constraints |
Y1: Entrapment Efficiency (EE%) | Maximize |
Y2: Particle size (PS) | Minimize |
Y3: Zeta potential (ZP) | In-range |
Y4: Permeability Coefficient (Kp) | Maximize |
Y5: Residence time (RT) | In-range |
Runs | Factors (Independent Variables) | Responses (Dependent Variables) | |||||||
---|---|---|---|---|---|---|---|---|---|
PC: CA Molar Ratio | EH: T. Lipids Molar Ratio | TMC Conc w/v | Y1:EE (%) | Y2: PS (nm) | Y3:ZP (mV) | Y4: Kp (cm/h) | Y5: RT (s) | DLC (%) | |
F1 | 1:1 | 0.25: 1 | 0.25 | 41.63 ± 3.62 | 293.86 ± 18.32 | 26.23 ± 3.26 | 3.24 | 123 ± 12 | 5.4 ± 0.6 |
F2 | 1:1 | 0.25: 1 | 0.50 | 35.42 ± 3.84 | 361.46 ± 22.48 | 28.61 ± 4.52 | 2.92 | 196 ± 16 | 3.6 ± 0.3 |
F3 | 1:1 | 0.50: 1 | 0.25 | 55.78 ± 2.58 | 325.23 ± 30.57 | 25.48 ± 4.68 | 3.91 | 114 ± 11 | 13.2 ± 1.2 |
F4 | 1:1 | 0.50: 1 | 0.50 | 46.66 ± 3.12 | 403.24 ± 26.27 | 27.97 ± 3.89 | 3.63 | 208 ± 20 | 8.9 ± 0.9 |
F5 | 1.5:1 | 0.38: 1 | 0.38 | 73.52 ± 2.51 | 187.12 ± 16.81 | 32.48 ± 4.87 | 5.35 | 195 ± 15 | 11.6 ± 1.5 |
F6 | 1.5:1 | 0.38: 1 | 0.38 | 74.63 ± 1.96 | 184.52 ± 21.24 | 32.43 ± 2.95 | 4.90 | 203 ± 23 | 11.3 ± 1.6 |
F7 | 1.5:1 | 0.38: 1 | 0.38 | 78.61 ± 2.37 | 192.24 ± 20.85 | 33.15 ± 3.50 | 5.17 | 176 ± 18 | 11.7 ± 0.9 |
F8 | 2:1 | 0.25: 1 | 0.25 | 65.52 ± 2.82 | 136.45 ± 14.69 | 32.14 ± 3.72 | 5.42 | 132 ± 16 | 8.1 ± 0.8 |
F9 | 2:1 | 0.25: 1 | 0.50 | 57.48 ± 3.27 | 167.81 ± 19.27 | 34.56 ± 4.22 | 4.61 | 231 ± 24 | 5.7 ± 0.4 |
F10 | 2:1 | 0.50: 1 | 0.25 | 79.73 ± 2.96 | 178.42 ± 21.36 | 32.12 ± 3.28 | 5.68 | 120 ± 13 | 17.8 ± 2.1 |
F11 | 2:1 | 0.50: 1 | 0.50 | 66.49 ± 3.08 | 208.76 ± 18.96 | 33.92 ± 3.66 | 4.16 | 228 ± 19 | 12.3 ± 1.1 |
Source | PS (nm) | EE% | ZP | Kp | RT | |||||
---|---|---|---|---|---|---|---|---|---|---|
F | p-Value | F | p-Value | F | p-Value | F | p-Value | F | p-Value | |
Model | 733.64 | <0.0001 | 49.48 | 0.0043 | 109.95 | 0.0013 | 19.51 | 0.0168 | 22.93 | 0.0133 |
A: PC: CA molar ratio | 3809.33 | <0.0001 | 201.52 | 0.0008 | 574.99 | 0.0002 | 82.56 | 0.0028 | 4.56 | 0.1223 |
B: EH: T. lipids molar ratio | 193.57 | 0.0008 | 59.14 | 0.0046 | 4.04 | 0.1379 | 3.07 | 0.1780 | 0.13 | 0.7385 |
C: TMC Conc (mg) | 341.54 | 0.0003 | 33.55 | 0.0102 | 79.47 | 0.0030 | 18.62 | 0.0229 | 130.27 | 0.0014 |
AB3 | 0.4479 | 0.7540 | 0.5257 | 0.1038 | 0.6210 | |||||
AC | 0.0049 | 0.4160 | 0.5691 | 0.0841 | 0.3094 | |||||
BC | 0.4640 | 0.2896 | 0.6513 | 0.3965 | 0.4274 | |||||
Lack of Fit | 0.4117 | 0.7908 | 0.5867 | 0.3623 | 0.7886 | |||||
Adequate precision | 78.035 | 22.950 | 28.941 | 12.565 | 11.538 | |||||
R2 | 0.9993 | 0.9900 | 0.9955 | 0.9750 | 0.9787 | |||||
Adjusted R2 | 0.9980 | 0.9700 | 0.9864 | 0.9250 | 0.9360 | |||||
Predicted R2 | 0.9861 | 0.9681 | 0.9503 | 0.9662 | 0.8989 | |||||
SD | 3.97 | 2.23 | 0.36 | 0.24 | 11.59 | |||||
%CV | 1.65 | 3.64 | 1.17 | 5.39 | 6.62 |
PS (nm) | EE% | ZP | Kp | RT | |
---|---|---|---|---|---|
Intercept | +259.40 | +56.09 | +30.13 | +4.20 | +169.00 |
A: PC: CA molar ratio | −86.54 | +11.22 | +3.06 | +0.77 | +8.75 |
B: EH: T. lipids molar ratio | +19.51 | +6.08 | −0.26 | +0.15 | −1.50 |
C: TMC Conc (mg) | +25.91 | −4.58 | +1.14 | −0.37 | +46.75 |
A × B | +1.22 | −0.27 | +0.091 | −0.20 | −2.25 |
A × C | −10.49 | −0.74 | −0.081 | −0.22 | +5.00 |
B × C | +1.17 | −1.01 | −0.064 | −0.084 | +3.75 |
EE% | PS (nm) | ZP (mV) | |
---|---|---|---|
At zero time | 79.73 ± 2.96 | 178.42 ± 21.36 | 32.12 ± 3.28 |
After 3 months stored at 25 ± 2 °C and controlled humidity of 75% | 78.85 ± 2.06 | 180.92 ± 19.19 | 32.44 ± 1.88 |
After 3 months stored at 25 ± 2 °C and controlled humidity of 75% | 78.63 ± 1.96 | 183.12 ± 1.36 | 31.92 ± 2.14 |
Formula | Cmax (ng/g) | Tmax (min) | AUC(0–8) (ng/g.hr) | DTI | DTE% | DTP% | |||
---|---|---|---|---|---|---|---|---|---|
Plasma | Brain | Plasma | Brain | Plasma | Brain | ||||
EH emulsomes | 143 ± 22 # | 271 ± 56 *# | 60 | 30 # | 588 ± 103 *# | 582 ± 112 *# | 4.1 ± 0.35 # | 407.6 ± 35.7 # | 75.5 ± 4.8 # |
i.n EH solution | 55 ± 17 | 85 ± 18 * | 60 | 60 | 243 ± 56 * | 90 ± 23 * | 1.5 ± 0.22 | 152.4 ± 22.4 | 34.4 ± 1.6 |
i.v. EH solution | - | 189 ± 38 | - | 30 | 950 ± 89 | 231 ± 41 | - | - | - |
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Abo El-Enin, H.A.; Mostafa, R.E.; Ahmed, M.F.; Naguib, I.A.; A. Abdelgawad, M.; Ghoneim, M.M.; Abdou, E.M. Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms. Pharmaceutics 2022, 14, 410. https://doi.org/10.3390/pharmaceutics14020410
Abo El-Enin HA, Mostafa RE, Ahmed MF, Naguib IA, A. Abdelgawad M, Ghoneim MM, Abdou EM. Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms. Pharmaceutics. 2022; 14(2):410. https://doi.org/10.3390/pharmaceutics14020410
Chicago/Turabian StyleAbo El-Enin, Hadel A., Rasha E. Mostafa, Marwa F. Ahmed, Ibrahim A. Naguib, Mohamed A. Abdelgawad, Mohammed M. Ghoneim, and Ebtsam M. Abdou. 2022. "Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms" Pharmaceutics 14, no. 2: 410. https://doi.org/10.3390/pharmaceutics14020410
APA StyleAbo El-Enin, H. A., Mostafa, R. E., Ahmed, M. F., Naguib, I. A., A. Abdelgawad, M., Ghoneim, M. M., & Abdou, E. M. (2022). Assessment of Nasal-Brain-Targeting Efficiency of New Developed Mucoadhesive Emulsomes Encapsulating an Anti-Migraine Drug for Effective Treatment of One of the Major Psychiatric Disorders Symptoms. Pharmaceutics, 14(2), 410. https://doi.org/10.3390/pharmaceutics14020410