The Potential Synergistic Activity of Zolmitriptan Combined in New Self-Nanoemulsifying Drug Delivery Systems: ATR-FTIR Real-Time Fast Dissolution Monitoring and Pharmacodynamic Assessment
| Autor: | Abd El-Halim, Shady M, Mamdouh, Mohamed A, Eid, Sherif M, Ibrahim, Bassant M M, Aly Labib, Dina A, Soliman, Sara M |
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| Rok vydání: | 2021 |
| Předmět: |
Biophysics
Pharmaceutical Science Administration Oral Biological Availability Bioengineering Lavender oil Zolmitriptan Pharmacology algesia Biomaterials Surface-Active Agents Drug Delivery Systems International Journal of Nanomedicine ZMT-SNEDDS Drug Discovery Spectroscopy Fourier Transform Infrared medicine Distribution (pharmacology) Potency Animals Dissolution testing Particle Size Oxazolidinones Original Research Chemistry Organic Chemistry General Medicine real-time monitoring acute migraine nitroglycerin Acute toxicity Tryptamines Rats Drug Liberation Solubility Pharmacodynamics Drug delivery activity cage Nanoparticles Emulsions medicine.drug |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Purpose The current work aimed to overcome the poor permeability and undesirable adverse effects of Zolmitriptan (ZMT) and to increase its efficacy in the treatment of acute migraine by exploiting the synergistic effect of the essential oil, lavender, to fabricate ZMT self-nanoemulsifying drug delivery systems (ZMT-SNEDDS). Methods ZMT-SNEDDS were fabricated based on full factorial design (32) to statistically assess the impact of oil and surfactant concentrations on the nanoemulsion globule size, zeta potential and percentage drug dissolution efficiency. An ATR-FTIR method was developed and validated for continuous real-time monitoring of ZMT dissolution and permeation. The dose of the optimized ZMT-SNEDDS used in the efficacy study was selected according to the acute toxicity study. The efficacy study was performed on migraineous rats induced by nitroglycerin and was evaluated by the activity cage and thermal tests, electroencephalogram, electroconvulsive stimulation, and biochemical analysis of brain tissue. Finally, histopathological and immunohistochemical examinations of the cerebra were carried out. Results Upon dilution, the optimized ZMT-SNEDDS (F5) exhibited nanosized spherical droplets of 19.59±0.17 nm with narrow size distribution, zeta potential (−23.5±1.17mV) and rapid emulsification characteristics. ATR-FTIR spectra elucidated the complete time course of dissolution and permeation, confirming F5 superior performance. Moreover, ZMT-SNEDDS (F5) showed safety in an acute toxicity study. ZMT concentration in rat brain tissues derived from F5 was lower compared to that of ZMT solution, yet its effect was better on the psychological state, algesia, as well as maintaining normal brain electrical activity and delayed convulsions. It counteracted the cerebral biochemical alternations induced by nitroglycerin, which was confirmed by histopathological examination. Conclusion In a nutshell, these findings corroborated the remarkable synergistic efficacy and the high potency of lavender oil-based ZMT-SNEDDS in migraine management compared to the traditional zolmitriptan solution. Graphical abstract |
| Databáze: | OpenAIRE |
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