Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemical and Reagents
2.2. Formulation of Nanocarriers
2.2.1. Screening of Solid Lipids
2.2.2. Preparation of SLNs
2.2.3. Optimization of SLNs Formulations
2.2.4. High-Performance Liquid Chromatography (HPLC)
2.3. Physicochemical Characterizations
2.3.1. Micromeritics and Surface Charge
2.3.2. Entrapment Efficiency and Drug Loading Capacity
2.4. FTIR and XRD Analyses
2.5. Morphological Attributes
2.6. In Vitro Drug Release
2.7. Stability Studies
2.8. Culture of Caco-2 Cells and Caco-2 Cells-Based Assays
2.8.1. In Vitro Caco-2 Cytotoxicity Assay
2.8.2. Cellular Permeability Studies
2.9. In Vivo Studies
2.9.1. Animal Care
2.9.2. Pharmacokinetic Studies
2.9.3. Antinociceptive and Anti-Inflammatory Activities
Evolution of Paw Edema
Assessment of Thermal Hyperalgesia
Tail Flick Test
Tissue (Paw) Level Determination of Antioxidants and Oxidative Stress Markers
Tissue Level Determination of Pro-Inflammatory Cytokines
Histological Studies
2.10. Statistical Analysis
3. Results
3.1. Physicochemical Screening of SLNs and Selection of SLN2 as the Optimized Formulation
3.2. Stability of PTZ-Loaded SLN2
3.3. In Vitro PTZ Drug Release from PTZ-Loaded SLN2 (Simulated Conditions)
3.4. Cytotoxicity and Cellular Permeability of PTZ-Loaded SLN2 in Caco-2 Cells
3.5. Pharmacokinetic Studies in Wistar Rats
3.6. Carrageenan-Induced Paw Edema, Thermal Hyperalgesia, and Tail Flick Response in Wistar Rats
3.7. Carrageenan-Induced Oxidative stress in Wistar Rats
3.8. Carrageenan-Induced Pro-Inflammatory Cytokines in Wistar Rats
3.9. PTZ-Loaded SLN2 Reverts the Carrageenan-Induced Histological Changes in Wistar Rats
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SLNs Code | Lipid Type | Surfactant Type | Surfactant (%) | Acetone: DCM | Lecithin: Lipid | HG Speed (rpm) | HG Time (min) |
---|---|---|---|---|---|---|---|
SLN1 | Stearic acid | Tween 20 | 3 | 1:2 | 2:7 | 15,000 | 15 |
SLN2 | Cetyl alcohol | Tween 80 | 3 | 1:2 | 1:8 | 16,000 | 15 |
SLN3 | Cetyl alcohol | Tween 80 | 2 | 1:2 | 2:7 | 16,000 | 10 |
SLN4 | Stearic acid | Tween 20 | 2 | 1:1 | 2:7 | 16,000 | 15 |
SLN5 | Stearic acid | Tween 20 | 2 | 1:2 | 1:8 | 15,000 | 10 |
SLN6 | Cetyl alcohol | Tween 80 | 2 | 1:1 | 1:8 | 15,000 | 15 |
SLN7 | Cetyl alcohol | Tween 20 | 3 | 1:1 | 1:8 | 16,000 | 10 |
SLN8 | Stearic acid | Tween 80 | 3 | 1:1 | 2:7 | 15,000 | 10 |
Code | PS (nm) | ZP (mV) | PDI | EE% | LC% |
---|---|---|---|---|---|
Experimental SLN1 | 189.40 ± 2.05 | −4.47 ± 0.35 | 0.44 ± 0.04 | 68.67 ± 0.57 | 1.70 ± 0.30 |
SLN2 | 137.70 ± 1.01 | −16.60 ± 0.51 | 0.28 ± 0.005 | 86.00 ± 3.60 | 10.27 ± 0.50 |
SLN3 | 249.70 ± 1.65 | −23.33 ± 0.90 | 0.38 ± 0.015 | 42.67 ± 1.52 | 1.13 ± 0.12 |
SLN4 | 172.00± 8.18 | −11.77 ± 0.50 | 0.57 ± 0.064 | 75.67 ± 2.08 | 1.30 ± 0.26 |
SLN5 | 237.00 ± 4.05 | −5.33 ± 0.30 | 0.53 ± 0.025 | 47.47 ± 1.50 | 2.37 ± 0.32 |
SLN6 | 261.40 ± 3.50 | −19.32 ± 0.91 | 0.23 ± 0.015 | 78.33 ± 1.52 | 1.77 ± 0.20 |
SLN7 | 154.70 ± 3.80 | −10.88 ± 0.37 | 0.74 ± 0.040 | 70.67 ± 2.09 | 4.03 ± 0.20 |
SLN8 | 146.80 ± 3.29 | −5.39 ± 0.63 | 0.17 ± 0.035 | 43.67 ± 3.21 | 2.73 ± 0.70 |
Predicted SLNs | 120.12 ± 10.49 | −13.52 ± 4.95 | 0.45 ± 0.07 | 61.87 ± 5.75 | 25.00 ± 3.98 |
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Khan, Z.U.; Razzaq, A.; Khan, A.; Rehman, N.U.; Khan, H.; Khan, T.; Khan, A.U.; Althobaiti, N.A.; Menaa, F.; Iqbal, H.; et al. Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model. Pharmaceutics 2022, 14, 409. https://doi.org/10.3390/pharmaceutics14020409
Khan ZU, Razzaq A, Khan A, Rehman NU, Khan H, Khan T, Khan AU, Althobaiti NA, Menaa F, Iqbal H, et al. Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model. Pharmaceutics. 2022; 14(2):409. https://doi.org/10.3390/pharmaceutics14020409
Chicago/Turabian StyleKhan, Zaheer Ullah, Anam Razzaq, Ahsan Khan, Naeem Ur Rehman, Hira Khan, Taous Khan, Ashraf Ullah Khan, Norah A. Althobaiti, Farid Menaa, Haroon Iqbal, and et al. 2022. "Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model" Pharmaceutics 14, no. 2: 409. https://doi.org/10.3390/pharmaceutics14020409
APA StyleKhan, Z. U., Razzaq, A., Khan, A., Rehman, N. U., Khan, H., Khan, T., Khan, A. U., Althobaiti, N. A., Menaa, F., Iqbal, H., & Khan, N. U. (2022). Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model. Pharmaceutics, 14(2), 409. https://doi.org/10.3390/pharmaceutics14020409