Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: I. Optimization, Characterization, Brain Localization, and Cytotoxic Studies.
Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: I. Optimization, Characterization, Brain Localization, and Cytotoxic Studies.
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DOI：
10.3390/pharmaceutics15071805
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发表时间：
2023-06-23
期刊：
影响因子：
5.4
通讯作者：
Eid, Hussein M.
中科院分区：
文献类型：
--
作者：
Elkomy, Mohammed H.;Zaki, Randa Mohammed;Alsaidan, Omar A.;Elmowafy, Mohammed;Zafar, Ameeduzzafar;Shalaby, Khaled;Abdelgawad, Mohamed A.;El-Ela, Fatma I. Abo;Rateb, Mostafa E.;Naguib, Ibrahim A.;Eid, Hussein M.
许多神经系统疾病的病理生理学都与大脑中自由基产生的增加有关。槲皮素（QER）是一种营养化合物，可以保护大脑免受氧化应激诱导的神经变性。尽管如此，它的低口服生物利用度减少了脑传递。因此，本研究旨在制备装载QER的转移体纳米囊泡（QER- tfs）原位凝胶，用于QER经鼻入脑给药。本研究探讨脂质含量、边缘激活剂（edge activator， EA）含量和EA类型对鼻黏膜囊泡直径、包埋和累计渗透量（24 h）的影响。在对其物理和形态特性进行评估后，将最佳配方整合到热敏凝胶中。优化后的QER-TFS评价显示纳米囊泡（171.4±3.4 nm）为球形，包封效率为78.2±2.8%。QER-TFS的短期稳定性和高zeta电位值（−32.6±1.4 mV）证实了其高稳定性。与QER溶液相比，优化后的QER- tfs原位凝胶制剂具有缓释作用，且鼻黏膜通透性增强。大鼠脑的CT扫描显示，在所有治疗组的大脑中都有金纳米粒子（GNPs）的积累，在给予转移体凝胶的大鼠中发现了更高水平的GNPs。此外，对PCS-200-014细胞的体外研究显示，QER-TFS原位凝胶的细胞毒性很小。基于这些结果，发育的转移体纳米囊泡可能是经鼻内途径靶向QER脑的合适纳米载体。
Numerous neurological disorders have a pathophysiology that involves an increase in free radical production in the brain. Quercetin (QER) is a nutraceutical compound that shields the brain against oxidative stress-induced neurodegeneration. Nonetheless, its low oral bioavailability diminishes brain delivery. Therefore, the current study aimed to formulate QER-loaded transferosomal nanovesicles (QER-TFS) in situ gel for QER brain delivery via the intranasal route. This study explored the impacts of lipid amount, edge activator (EA) amount, and EA type on vesicle diameter, entrapment, and cumulative amount permeated through nasal mucosa (24 h). The optimum formulation was then integrated into a thermosensitive gel after its physical and morphological characteristics were assessed. Assessments of the optimized QER-TFS showed nanometric vesicles (171.4 ± 3.4 nm) with spherical shapes and adequate entrapment efficiency (78.2 ± 2.8%). The results of short-term stability and high zeta potential value (−32.6 ± 1.4 mV) of QER-TFS confirmed their high stability. Compared with the QER solution, the optimized QER-TFS in situ gel formulation exhibited sustained release behavior and augmented nasal mucosa permeability. CT scanning of rat brains demonstrated the buildup of gold nanoparticles (GNPs) in the brains of all treatment groups, with a greater level of GNPs noted in the rats given the transferosomal gel. Additionally, in vitro studies on PCS-200-014 cells revealed minimal cytotoxicity of QER-TFS in situ gel. Based on these results, the developed transferosomal nanovesicles may be a suitable nanocarrier for QER brain targeting through the intranasal route.
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影响因子：
5.8
作者：
Dragicevic-Curic, Nina;Friedrich, Manfred;Fahr, Alfred
通讯作者：
Fahr, Alfred
影响因子：
6
作者：
通讯作者：
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DOI：
10.3390/ph15030281
发表时间：
2022-02-24
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Abo El-Enin HA;Elkomy MH;Naguib IA;Ahmed MF;Alsaidan OA;Alsalahat I;Ghoneim MM;Eid HM
通讯作者：
Eid HM
影响因子：
6
作者：
Elkomy, Mohammed H.;El Menshawe, Shahira F.;Elkarmalawy, Marwa H.
通讯作者：
Elkarmalawy, Marwa H.
影响因子：
5.4
作者：
Eissa, Essam M.;Elkomy, Mohammed H.;Eid, Hussein M.;Ali, Adel A.;Abourehab, Mohammed A. S.;Alsubaiyel, Amal M.;Naguib, Ibrahim A.;Alsalahat, Izzeddin;Hassan, Amira H.
通讯作者：
Hassan, Amira H.