Zolmitriptan niosomal transdermal patches: combating migraine via epigenetic and endocannabinoid pathways and reversal of migraine hypercoagulability.

Autor: Abou Youssef NAH; Department of Pharmaceutics and Pharmaceutical technology, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia street, beside Green Plaza Complex , Alexandria, 21648, Egypt., Labib GS; Department of Pharmaceutics and Pharmaceutical technology, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia street, beside Green Plaza Complex , Alexandria, 21648, Egypt.; Faculty of Pharmacy, Alamein International University, Alamein, Matrouh, 51718, Egypt., Kassem AA; Department of Pharmaceutics and Pharmaceutical technology, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia street, beside Green Plaza Complex , Alexandria, 21648, Egypt. abeer.kassem@pua.edu.eg., El-Mezayen NS; Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, 21648, Egypt.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 Nov 05. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1007/s13346-024-01731-6
Abstrakt: Conventional zolmitriptan (ZOL) has limited oral bioavailability, many adverse effects, and poor membrane penetrability that negatively influences its accessibility to its 5-HT 1B/1D receptor binding pocket, located transmemberanous. This work aimed at preparing transdermal ZOL-nanoformulation (niosomes) to surpass these limitations and to explore novel antimigraine mechanisms for ZOL via modulation of the epigenetically-altered chronification genes (RAMP-1, NPTX-2) or microRNAs and affecting the endocannabinoid CB-1/MAPK pathway. The prepared ZOL niosomes (F sp60/6-1:1 ) exhibited %EE of 57.28%, PS of 472.3 nm, PDI of 0.366, and ZP of -26 mV were cast into patch with content uniformity of 93.12%, maintained endurance after 200-times folding, no interaction between its components (FT-IR), a biphasic release pattern and good stability after storage at 4 °C for 6 months. In-vivo ZOL-patch application in rats with nitroglycerin-induced migraine showed significant management of migraine pain symptoms and photophobia assessed behaviorally, decreased brain levels of the trigeminal neuronal activation marker (c-fos), the migraine pain neurotransmitter (CGRP) and the serum levels of different migraine pain markers (substance P, nitric-oxide, and TNF-α). It also significantly decreased RAMP-1, NPTX-2, miR-382-5p, and CB-1/MAPK gene expression reflecting improved efficacy and brain receptors delivery to a much greater extent than conventional ZOL has done. Additionally, this nanoformulation significantly opposed migraine-induced platelet activation and hypercoagulable status in both central and peripheral circulations as evidenced by the significant decrease in adenosine diphosphate, thrombin, factor X, CD41, and Von-Willebrand factor levels assessed peripherally and centrally. TPF sp60/6-1:1 significantly improved ZOL efficacy and accessibility to brain-receptors to a much greater extent than conventional ZOL-solution.KeywordsEndocannabinoid receptors; Epigenetically-altered genes; Hemostatic pathways; Niosomal patch; Transdermal; Zolmitriptan.
(© 2024. The Author(s).)
Databáze: MEDLINE
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