Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways
Abstract
:1. Introduction
2. Materials and Methods
2.1. Preparation of Chitosomes (Chitosan-Coated Anionic Liposomes) (CS-NPs)
2.2. Physicochemical Characterization of CS-NPs
2.2.1. Particle size, Zetapotential, and Polydispersity Index Measurement
2.2.2. Determination of Entrapment Efficiency (EE%)
2.2.3. Transmission Electron Microscopy
2.2.4. In Vitro Release Study
2.2.5. Release Kinetics of Chitosan Nanoparticles
2.2.6. Stability Study
2.2.7. In Vitro Mucoadhesion Test
2.3. In Vivo Studies
2.3.1. Animals
2.3.2. Induction of Sporadic Alzheimer’s Disease (SAD)
2.3.3. Experimental Design
2.3.4. Intranasal Administration
2.3.5. Behavioral Assessment
Y-Maze
Morris Water Maze (MWM)
2.3.6. Histopathology
2.3.7. Immunohistochemistry
2.3.8. Measurement of Biochemical Parameters
Estimation of Oxidative Stress Markers (MDA, GSH, and NRF2)
Estimation of Pro-Inflammatory Mediators (NOS, COX-2, NF-Κβ, and TNF-α)
Determination of Mouse MMP-9(Matrix Metalloproteinase 9)
Estimation of Amyloidogenesis and Tauopathy (Aβ1-42 and Tau)
Estimation of The Mouse cAMP Response Element Binding Protein (CREB) Transcription Factors
2.3.9. Safety Studies
2.3.10. Statistical Analysis
3. Results and Discussion
3.1. Preparation and Characterization of Chitosomes (CHS)
3.2. Transmission Electron Microscopy (TEM)
3.3. In Vitro Release Study and Release Kinetics
3.4. In Vitro Mucoadhesion Test
3.5. In Vivo Study
3.5.1. Behavioral Test
Y-Maze Test
Morris Water Maze (MWM) and Mean Escape Latency (MEL)
Morris Water Maze (MWM) and The Time Spent in The Target Quadrant
3.5.2. Histopathology
3.5.3. Immunohistochemistry
3.5.4. Biochemical Parameters
Estimation of Oxidative Stress Markers (MDA, GSH and NRF2)
Estimation of Pro-Inflammatory Mediators (NOS, COX-2, NF-κβ, and TNF-α)
Estimation of Aβ1-42 and Tau
Estimation of MMP9
Estimation of Transcription Factors (CREB)
3.5.5. Safety Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ingredients (%w/v) | F1 | F2 | F3 | F4 | F5 | F6 |
---|---|---|---|---|---|---|
Phosphatidyl choline | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 |
Cholesterol | 25 | 25 | 25 | 25 | 25 | 25 |
Phosphatidyl serine | 3 | 3 | 3 | 3 | 3 | 3 |
Luteolin | ----- | 20 a | 40 b | 20 | 20 | 20 |
Chitosan | ----- | ----- | ----- | 2 | 4 | 8 |
Formulation Code | Particle Size (nm) ± SD | PDI± SD | Zeta Potential (mV) ± SD | Entrapment Efficiency% ± SD |
---|---|---|---|---|
F1 (Empty Lip.) | 184.6 ± 1.85 | 0.3014 ± 0.06 | −24.9 ± 4.21 | NA |
F2 (Lip-LUT20 a) | 212.3 ± 2.18 | 0.398 ± 0.09 | −33.1 ± 2.11 | 80.6 ± 1.28 |
F3 (Lip-LUT40 b) | 320.0 ± 4.23 | 0.407 ± 0.25 | −31.6 ± 1.48 | 77.9 ± 1.33 |
F4 (LUT-CHS2% c) | 347.2 ± 1.84 | 0.419 ± 0.04 | 28 ± 2.94 | 79.2 ± 2.54 |
F5 (LUT-CHS4% d) | 412.8 ± 3.28 | 0.378 ± 0.07 | 37.4 ± 2.13 | 86.6 ± 2.05 |
F6 (LUT-CHS8% e) | 473.1 ± 2.14 | 0.274 ± 0.03 | 36.2 ± 3.04 | 81.5 ± 1.77 |
Months | Size (nm) | PDI | Zeta (mv) | EE (%) |
---|---|---|---|---|
0 | 412.8 ± 3.28 | 0.378 ± 0.07 | 37.4 ± 2.13 | 86.6 ± 2.05 |
3 | 426.1 ± 3.01 | 0.400 ± 0.11 | 35.8 ± 3.17 | 85.1 ± 3.01 |
6 | 435.3 ± 2.81 | 0.415 ± 0.56 | 34.3 ± 3.04 | 82.8 ± 1.15 |
Model Name and Equation | Parameters | Values |
---|---|---|
Higuchi * F = kH √t | Rsqr_adj | 0.909 |
MSE | 94.59 | |
kH | 21.38 | |
MSC | 1.86 | |
Hixson-Crowell * | Rsqr_adj | 0.975 |
MSE | 27.49 | |
k1/3 | 0.043 | |
MSC | 3.09 | |
Korsmeyer-Peppas * | Rsqr_adj | 0.900 |
MSE | 103.7 | |
n | 0.462 | |
kp | 23.43 | |
MSC | 1.68 | |
Weibull * ) | Rsqr_adj | 0.992 |
MSE | 16.49 | |
0.900 | ||
MSC | 3.478 |
Number of Amyloid Plaques (High Microscopic Field) | |
---|---|
Group (1) | ــــــــــــــــــــــ |
Group (2) | 6.2 ± 0.41 c |
Group (3) | 2.6 ± 0.4 b |
Group (4) | 1.4 ± 0.26 a |
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Abbas, H.; Sayed, N.S.E.; Youssef, N.A.H.A.; M. E. Gaafar, P.; Mousa, M.R.; Fayez, A.M.; Elsheikh, M.A. Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways. Pharmaceutics 2022, 14, 1003. https://doi.org/10.3390/pharmaceutics14051003
Abbas H, Sayed NSE, Youssef NAHA, M. E. Gaafar P, Mousa MR, Fayez AM, Elsheikh MA. Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways. Pharmaceutics. 2022; 14(5):1003. https://doi.org/10.3390/pharmaceutics14051003
Chicago/Turabian StyleAbbas, Haidy, Nesrine S El Sayed, Nancy Abdel Hamid Abou Youssef, Passent M. E. Gaafar, Mohamed R. Mousa, Ahmed M. Fayez, and Manal A Elsheikh. 2022. "Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways" Pharmaceutics 14, no. 5: 1003. https://doi.org/10.3390/pharmaceutics14051003
APA StyleAbbas, H., Sayed, N. S. E., Youssef, N. A. H. A., M. E. Gaafar, P., Mousa, M. R., Fayez, A. M., & Elsheikh, M. A. (2022). Novel Luteolin-Loaded Chitosan Decorated Nanoparticles for Brain-Targeting Delivery in a Sporadic Alzheimer’s Disease Mouse Model: Focus on Antioxidant, Anti-Inflammatory, and Amyloidogenic Pathways. Pharmaceutics, 14(5), 1003. https://doi.org/10.3390/pharmaceutics14051003