Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Amphiphilic Polymer PVP-OD4000 Preparation
2.3. Indomethacin-Loaded PVP-OD4000 Nanoparticles Preparation
2.4. Characterization of PVP-OD4000 Nanoparticles
2.5. Characterization of IMC Release
2.6. Animals
2.7. Pharmacokinetics Study
2.8. Carrageenan-Induced Edema Acute Model
2.9. Complete Freund’s Adjuvant-Induced Edema Sub-Chronic Model
2.10. Complete Freund’s Adjuvant-Induced Arthritis Model
2.11. Ulcerogenic Activity Study
2.12. Determination of Serum Cytokine Levels
2.13. Statistical Analysis
3. Results and Discussion
3.1. IMC-Loaded PVP-OD4000 Nanoparticles Preparation and Characterization
3.2. In Vivo Pharmacokinetics and Biodistribution of Free IMC and IMC-Loaded-PVP-OD4000 Nanoparticles
3.3. The Effect of Free IMC and IMC-Loaded-PVP-OD4000 Nanoparticles on Carrageenan-Induced Acute Edema Model
3.4. The Effect of Free IMC and IMC-Loaded-PVP-OD4000 Nanoparticles on Complete Freund’s Adjuvant-Induced Edema Sub-Chronic Model
3.5. The Effect of Free IMC and IMC-Loaded PVP-OD4000 Nanoparticles on Complete Freund’s Adjuvant-Induced Arthritis Model
3.6. The Effect of Free IMC and IMC-Loaded PVP-OD4000 Nanoparticles on Cytokine Release in Complete Freund’s Adjuvant-Induced Arthritis Model
3.7. Ulcerogenic Activity Study
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Nanoparticle Type | IMC/Polymer Weight Ratio | Particle Size (nm) | Particle PDI | Zeta Potential (mV) | IMC DLE (%) | IMC Content (%) |
---|---|---|---|---|---|---|
PVP-OD4000 | 0.0:1.0 | 124.7 ± 6.6 | 0.132 ± 0.022 | −9.57 ± 0.79 | - | - |
IMC-loaded PVP-OD4000 | 0.25:1.0 | 98.6 ± 4.9 | 0.147 ± 0.036 | −7.15 ± 0.58 | 98.1 | 19.6 |
Pharmacokinetic Parameter | Free IMC | PVP-OD4000 + IMC |
---|---|---|
Cmax (μg/mL) | 51.82 ± 6.47 | 43.93 ± 5.08 |
tmax (h) | 0.9 ± 0.23 | 0.9 ± 0.23 |
λ (1/h) * | 0.082 ± 0.009 | 0.054 ± 0.014 |
AUC (μg∙h/mL) * | 516.70 ± 68.41 | 738.91 ± 110.16 |
AUMC (μg∙h2/mL) * | 5982.74 ± 1026.09 | 16026.23 ± 6121.12 |
VD (mL/kg) * | 202.63 ± 57.54 | 298.34 ± 39.89 |
Cl (mL/h) | 15.05 ± 2.12 | 15.12 ± 2.03 |
MRT (h) * | 11.61 ± 0.93 | 21.66 ± 4.51 |
Animal Group | Indomethacin Dose (mg/kg BW) | Paw Volume Difference (mL ± SEM a) | Paw Volume Increase (%) | Edema Inhibition I (%) |
---|---|---|---|---|
Group 1 (Control)—PBS b | 0 | 0.250 ± 0.004 | 139.8 | - |
Group 2 (Placebo)—PVP-OD4000 nanoparticles | 0 | 0.244 ± 0.009 | 136.5 | - |
Group 3—Free indomethacin | 3.0 | 0.108 ± 0.005 ** | 60.1 | 57.0 |
Group 4—Indomethacin-loaded PVP-OD4000 nanoparticles | 1.0 | 0.118 ± 0.007 ** | 65.6 | 53.1 |
Group 5—Indomethacin-loaded PVP-OD4000 nanoparticles | 3.0 | 0.052 ± 0.006 ** | 28.7 | 79.5 |
Animal Group | Indomethacin Dose (mg/kg BW) | Paw volume Difference (mL ± SEM a) | Paw Volume Increase (%) | Edema Inhibition I (%) |
---|---|---|---|---|
Group 1 (Control)—PBS b | 0 | 0.420 ± 0.006 | 208.6 | - |
Group 2 (Placebo)—PVP-OD4000 nanoparticles | 0 | 0.425 ± 0.008 | 211.1 | - |
Group 3—Free indomethacin | 3.0 | 0.278 ± 0.007 ** | 139.4 | 33.2 |
Group 4—Indomethacin-loaded PVP-OD4000 nanoparticles | 1.0 | 0.294 ± 0.006 ** | 147.1 | 29.5 |
Group 5—Indomethacin-loaded PVP-OD4000 nanoparticles | 3.0 | 0.122 ± 0.005 ** | 61.2 | 70.7 |
CAF-Induced | PVP-OD4000 | Free IMC | PVP-OD4000 + IMC | |
---|---|---|---|---|
TNF-α (mean ± SEM a) | 820 ± 96 | 786 ± 78 | 597 ± 92 * | 123 ± 48 ** |
IL-6 (mean ± SEM a) | 341 ± 34 | 292 ± 38 | 203 ± 44 * | 36 ± 18 ** |
IL-10 (mean ± SEM a) | 552 ± 57 | 621 ± 46 | 814 ± 141 * | 1846 ± 122 ** |
Animal Group | Indomethacin Dose (mg/kg BW) | Mean Ulcer Score ± SEM a | Paul’s Index (PI) |
---|---|---|---|
Group 1—PVP-OD4000 nanoparticles | 0 | 0 | 0 |
Group 2—Free indomethacin | 40.0 | 12.2 ± 1.31 | 12.8 |
Group 3—Indomethacin-loaded PVP-OD4000 nanoparticles | 40.0 | 6.7 ± 1.94 ** | 3.9 |
Group 4—Indomethacin-loaded PVP-OD4000 nanoparticles | 60.0 | 10.1 ± 2.27 * | 6.2 |
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Kuskov, A.; Nikitovic, D.; Berdiaki, A.; Shtilman, M.; Tsatsakis, A. Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study. Pharmaceutics 2022, 14, 925. https://doi.org/10.3390/pharmaceutics14050925
Kuskov A, Nikitovic D, Berdiaki A, Shtilman M, Tsatsakis A. Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study. Pharmaceutics. 2022; 14(5):925. https://doi.org/10.3390/pharmaceutics14050925
Chicago/Turabian StyleKuskov, Andrey, Dragana Nikitovic, Aikaterini Berdiaki, Mikhail Shtilman, and Aristidis Tsatsakis. 2022. "Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study" Pharmaceutics 14, no. 5: 925. https://doi.org/10.3390/pharmaceutics14050925
APA StyleKuskov, A., Nikitovic, D., Berdiaki, A., Shtilman, M., & Tsatsakis, A. (2022). Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study. Pharmaceutics, 14(5), 925. https://doi.org/10.3390/pharmaceutics14050925