Nose to brain delivery of naringin-loaded chitosan nanoparticles for potential use in oxaliplatin-induced chemobrain in rats: impact on oxidative stress, cGAS/STING and HMGB1/RAGE/TLR2/MYD88 inflammatory axes.

IF 5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Expert Opinion on Drug Delivery Pub Date : 2023-07-01 Epub Date: 2023-06-27 DOI:10.1080/17425247.2023.2228685
Diana M F Hanna, John Youshia, Sarah Farid Fahmy, Mina Y George
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Abstract

Objectives: Oxaliplatin induces chemobrain in cancer patients/survivors. Nutraceutical naringin has antioxidant and anti-inflammatory properties with low oral bioavailability. Our aim was to formulate naringin in chitosan nanoparticles for nose to brain delivery and assess its neuroprotective effect against oxaliplatin-induced chemobrain in rats.

Methods: Naringin chitosan nanoparticles were prepared by ionic gelation. Rats were administered oral naringin (80 mg/kg), intranasal naringin (0.3 mg/kg) or intranasal naringin-loaded chitosan nanoparticles (0.3 mg/kg). Naringin's neuroprotective efficacy was assessed based on behavioral tests, histopathology, and measuring oxidative stress and inflammatory markers.

Results: Selected nanoparticles formulation showed drug loading of 5%, size of 150 nm and were cationic. Intranasal naringin administration enhanced memory function, inhibited hippocampal acetylcholinesterase activity, and corrected oxaliplatin-induced histological changes. Moreover, it reduced malondialdehyde and elevated reduced glutathione hippocampal levels. Furthermore, it decreased levels of inflammatory markers: NF-kB and TNF-α by 1.25-fold. Upstream to this inflammatory status, intranasal naringin downregulated the hippocampal protein levels of two pathways: cGAS/STING and HMGB1/RAGE/TLR2/MYD88.

Conclusion: Intranasal naringin-loaded chitosan nanoparticles showed superior amelioration of oxaliplatin-induced chemobrain in rats at a dose 267-fold lower to that administered orally. The potential involvement of cGAS/STING and HMGB1/RAGE/TLR2/MYD88 pathways in the mechanistic process of either oxaliplatin-induced chemobrain or naringin-mediated neuroprotection was evidenced.

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从鼻腔到大脑输送柚皮苷壳聚糖纳米颗粒,用于奥沙利铂诱导的大鼠化疗脑:对氧化应激、cGAS/STING 和 HMGB1/RAGE/TLR2/MYD88 炎症轴的影响。
目的奥沙利铂会诱发癌症患者/幸存者的化疗脑。营养保健品柚皮苷具有抗氧化和抗炎特性,但口服生物利用度较低。我们的目的是将柚皮苷制成壳聚糖纳米颗粒,通过鼻腔向大脑输送,并评估其对奥沙利铂诱导的大鼠化学脑的神经保护作用:方法:采用离子凝胶法制备柚皮苷壳聚糖纳米颗粒。给大鼠口服柚皮苷(80 mg/kg)、鼻内注射柚皮苷(0.3 mg/kg)或鼻内注射柚皮苷壳聚糖纳米颗粒(0.3 mg/kg)。根据行为测试、组织病理学以及氧化应激和炎症标志物的测量来评估柚皮苷的神经保护功效:所选纳米颗粒配方的载药量为 5%,大小为 150 纳米,呈阳离子型。鼻内注射柚皮苷可增强记忆功能,抑制海马乙酰胆碱酯酶活性,纠正奥沙利铂诱导的组织学变化。此外,柚皮苷还能降低丙二醛的含量,提高还原型谷胱甘肽在海马中的含量。此外,它还降低了炎症标志物的水平:NF-kB和TNF-α的水平降低了1.25倍。在这种炎症状态的上游,鼻内注射柚皮苷可降低两个通路的海马蛋白水平:cGAS/STING 和 HMGB1/RAGE/TLR2/MYD88:结论:鼻内柚皮苷载壳聚糖纳米颗粒对大鼠奥沙利铂诱导的化脑有很好的改善作用,其剂量是口服剂量的267倍。cGAS/STING 和 HMGB1/RAGE/TLR2/MYD88 通路可能参与了奥沙利铂诱导的化学脑或柚皮苷介导的神经保护的机理过程。
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来源期刊
CiteScore
11.10
自引率
3.00%
发文量
104
审稿时长
3 months
期刊介绍: Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.
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