Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning
Abstract
:1. Introduction
2. Results
2.1. Transfersome Preparation and Characterization
2.2. In Vitro/Ex Vivo Release Study
2.3. In Vitro Toxicity Assessment
2.4. Evaluation of Effectiveness In Vivo
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Animals
4.3. Vesicle Preparation
4.4. Particle Zeta Potential and Size Distribution Analysis
4.5. Transmission Electron Microscopy (TEM)
4.6. Potentiometry
4.7. Drug Loading and Quantification of Encapsulation Efficiency (EE%)
4.8. In Vitro Substrate Release Rate Analysis
4.9. In Vitro Toxicity Assessment
4.10. Ex Vivo Substrate Release Studies
4.11. AChE Reactivation in Rat Blood
4.12. 2-PAM Pharmacokinetics in Rat Plasma
4.13. Rat Survival
4.14. Data Analysis and Statistics
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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System | Molar Ratio | Dh, nm | PdI | ζ, mV | Dh, nm | PdI | ζ, mV |
---|---|---|---|---|---|---|---|
1 Day | 2.5 Months | ||||||
PC | - | 113 ± 1 | 0.086 ± 0.009 | −14 ± 1 | 118 ± 1 | 0.119 ± 0.043 | −11 ± 1 |
PC/Tw20 | 1/0.2 | 107 ± 1 | 0.057 ± 0.002 | −11 ± 1 | 153 ± 13 | 0.232 ± 0.003 | −1 ± 1 |
PC/Tw20/C14PB | 1/0.2/0.02 | 111 ± 1 | 0.072 ± 0.019 | 21 ± 1 | 115 ± 1 | 0.071 ± 0.005 | 15 ± 1 |
PC/Tw20/C14PB | 1/0.2/0.025 | 117 ± 2 | 0.084 ± 0.004 | 29 ± 1 | 121 ± 1 | 0.075 ± 0.006 | 20 ± 1 |
PC/Tw20/C14PB | 1/0.2/0.04 | 120 ± 2 | 0.096 ± 0.003 | 38 ± 1 | 126 ± 1 | 0.083 ± 0.014 | 23 ± 1 |
PC/Tw20/C12PB | 1/0.2/0.025 | 110 ± 2 | 0.089 ± 0.015 | 23 ± 1 | 112 ± 1 | 0.076 ± 0.019 | 17 ± 1 |
PC/Tw20/C16PB | 1/0.2/0.025 | 116 ± 2 | 0.101 ± 0.004 | 24 ± 1 | 121 ± 1 | 0.093 ± 0.004 | 22 ± 1 |
System | Molar Ratio | EE, % | Dh, nm | PdI | ζ, mV | Dh, nm | PdI | ζ, mV |
---|---|---|---|---|---|---|---|---|
1 Day | 1 Month | |||||||
PC | - | 60.3 ± 2.8 | 118 ± 1 | 0.082 ± 0.012 | −2 ± 0.5 | 116 ± 2 | 0.115 ± 0.004 | −4 ± 1 |
PC/Tw20 | 1/0.2 | 55.3 ± 0.9 | 110 ± 1 | 0.061 ± 0.010 | −2 ± 0.2 | 139 ± 2 | 0.242 ± 0.006 | −3 ± 1 |
PC/Tw20/C14PB | 1/0.2/0.02 | 63.5 ± 3.3 | 105 ± 1 | 0.041 ± 0.009 | 12 ± 1 | 118 ± 1 | 0.111 ± 0.009 | 3 ± 1 |
PC/Tw20/C14PB | 1/0.2/0.025 | 64.7 ± 5.3 | 107 ± 2 | 0.061 ± 0.014 | 17 ± 1 | 103 ± 1 | 0.047 ± 0.017 | 5 ± 1 |
PC/Tw20/C14PB | 1/0.2/0.04 | 66.2 ± 2.1 | 114 ± 2 | 0.078 ± 0.009 | 24 ± 1 | 121 ± 2 | 0.099 ± 0.012 | 13 ± 1 |
PC/Tw20/C12PB | 1/0.2/0.025 | 56.9 ± 0.1 | 110 ± 1 | 0.076 ± 0.010 | 10 ± 1 | 110 ± 1 | 0.143 ± 0.020 | 6 ± 1 |
PC/Tw20/C16PB | 1/0.2/0.025 | 56.1 ± 1.5 | 117 ± 1 | 0.074 ± 0.016 | 9 ± 1 | 104 ± 1 | 0.085 ± 0.001 | 8 ± 1 |
System | Molar Ratio | IC50, mM * | |
---|---|---|---|
M-HeLa | WI-38 | ||
PC | - | 3.60 ± 0.28 | >5 |
PC/Tw20 | 1/0.2 | 1.68 ± 0.13 | 1.64 ± 0.12 |
PC/Tw20/C12PB | 1/0.2/0.025 | 0.48 ± 0.04 | 1.25 ± 0.10 |
PC/Tw20/C14PB | 1/0.2/0.025 | 0.51 ± 0.04 | 1.44 ± 0.11 |
PC/Tw20/C16PB | 1/0.2/0.025 | 0.75 ± 0.06 | 1.00 ± 0.08 |
Blood Sampling Time after Applying, h | Group of Treatment | |||
---|---|---|---|---|
POX, 1 h, n = 5 | POX, 1 h, + free 2- PAM, n = 5 | POX, 1 h, + PC/Tw20/2-PAM, n = 5 | POX, 1 h, + PC/Tw20/C14PB/2-PAM 1/0.2/0.025, n = 5 | |
AChE reactivation in rat erythrocytes, % | ||||
2 | 1.66 ± 3.79 p = 0.940 | 1.35 ± 3.40 p = 0.706 | 1.36 ± 5.57 p = 1.000 | 8.40 ± 7.52 p = 0.449 |
4 | 1.80 ± 3.74 p = 0.571 | 1.46 ± 5.95 p = 1.000 | 1.41 ± 5.20 p = 0.821 | 8.73 ± 7.18 p = 0.304 |
6 | 0.62 ± 3.16 p = 0.735 | 4.46 ± 9.30 p = 0.483 | 23.65 ± 7.23 p = 0.005 * | 11.98 ± 4.06 p = 0.05 |
24 | 2.85 ± 7.39 p = 0.678 | 7.25 ± 6.13 p = 0.404 | 24.2 ± 9.73 p = 0.021 * | 20.10 ± 11.80 p = 0.113 |
Group of Treatment | n/N * | % of Surviving Rats |
---|---|---|
POX | 0/20 | 0% |
POX + 2-PAM intravenously 10 min after POX | 11/20 | 55% |
PC/Tw20/2-PAM transdermally for 24 h + POX | 8/20 | 40% |
PC/Tw20/2-PAM transdermally for 24 h + POX + 2-PAM intravenously 10 min after POX | 18/20 | 90% |
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Vasileva, L.; Gaynanova, G.; Zueva, I.; Lyubina, A.; Amerhanova, S.; Buzyurova, D.; Babaev, V.; Voloshina, A.; Petrov, K.; Zakharova, L. Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning. Int. J. Mol. Sci. 2022, 23, 14992. https://doi.org/10.3390/ijms232314992
Vasileva L, Gaynanova G, Zueva I, Lyubina A, Amerhanova S, Buzyurova D, Babaev V, Voloshina A, Petrov K, Zakharova L. Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning. International Journal of Molecular Sciences. 2022; 23(23):14992. https://doi.org/10.3390/ijms232314992
Chicago/Turabian StyleVasileva, Leysan, Gulnara Gaynanova, Irina Zueva, Anna Lyubina, Syumbelya Amerhanova, Daina Buzyurova, Vasily Babaev, Alexandra Voloshina, Konstantin Petrov, and Lucia Zakharova. 2022. "Transdermal Delivery of 2-PAM as a Tool to Increase the Effectiveness of Traditional Treatment of Organophosphate Poisoning" International Journal of Molecular Sciences 23, no. 23: 14992. https://doi.org/10.3390/ijms232314992