Efficacy of intranasal delivery of VEGFR inhibitors to cervical lymph nodes for inhibiting tongue cancer metastasis in mice.

IF 3.9 4区 医学 Q1 PHARMACOLOGY & PHARMACY
Tomoyuki Furubayashi, Minori Kobayashi, Nao Hamada, Shuichi Kawashiri, Akiko Tanaka
{"title":"Efficacy of intranasal delivery of VEGFR inhibitors to cervical lymph nodes for inhibiting tongue cancer metastasis in mice.","authors":"Tomoyuki Furubayashi, Minori Kobayashi, Nao Hamada, Shuichi Kawashiri, Akiko Tanaka","doi":"10.1080/1061186X.2025.2531424","DOIUrl":null,"url":null,"abstract":"<p><p>Oral cancers frequently metastasise to adjacent cervical lymph nodes (CLNs), leading to systemic dissemination and poor prognosis. Intranasal (i.n.) drug delivery provides direct access to cervical lymphatics, enabling high local drug concentrations while minimising systemic exposure. This study evaluated the pharmacokinetics (PK) and anti-metastatic efficacy of two vascular endothelial growth factor receptor (VEGFR)-3 inhibitors - cediranib maleate (CDNB) and pazopanib hydrochloride (PPNB) - administered i.n. in a mouse model of tongue cancer. Pharmacokinetic analysis showed that i.n. delivery yielded significantly higher CLN concentrations of both drugs than intravenous administration, despite lower plasma levels. In tumour-bearing mice, i.n. CDNB markedly reduced the incidence of CLN metastasis (0.167) versus controls (0.875, <i>p</i> < .01) and was more effective than intraperitoneal CDNB (0.571) or i.n. PPNB (0.500). Although less potent, PPNB significantly reduced the number of metastatic CLNs (0.438, <i>p</i> < .05). CDNB exhibited superior and more consistent efficacy. The reduced effect of PPNB may reflect its lower dose - limited by solubility - and possible differences in target specificity. These findings highlight the potential of i.n. administration to deliver VEGFR-3 inhibitors to CLNs, suppress lymphangiogenesis and lymphatic metastasis, and reduce systemic toxicity. This approach may offer a non-invasive alternative to neck dissection in oral cancer.</p>","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":" ","pages":"1-10"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Targeting","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1061186X.2025.2531424","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Oral cancers frequently metastasise to adjacent cervical lymph nodes (CLNs), leading to systemic dissemination and poor prognosis. Intranasal (i.n.) drug delivery provides direct access to cervical lymphatics, enabling high local drug concentrations while minimising systemic exposure. This study evaluated the pharmacokinetics (PK) and anti-metastatic efficacy of two vascular endothelial growth factor receptor (VEGFR)-3 inhibitors - cediranib maleate (CDNB) and pazopanib hydrochloride (PPNB) - administered i.n. in a mouse model of tongue cancer. Pharmacokinetic analysis showed that i.n. delivery yielded significantly higher CLN concentrations of both drugs than intravenous administration, despite lower plasma levels. In tumour-bearing mice, i.n. CDNB markedly reduced the incidence of CLN metastasis (0.167) versus controls (0.875, p < .01) and was more effective than intraperitoneal CDNB (0.571) or i.n. PPNB (0.500). Although less potent, PPNB significantly reduced the number of metastatic CLNs (0.438, p < .05). CDNB exhibited superior and more consistent efficacy. The reduced effect of PPNB may reflect its lower dose - limited by solubility - and possible differences in target specificity. These findings highlight the potential of i.n. administration to deliver VEGFR-3 inhibitors to CLNs, suppress lymphangiogenesis and lymphatic metastasis, and reduce systemic toxicity. This approach may offer a non-invasive alternative to neck dissection in oral cancer.

经鼻给药VEGFR抑制剂抑制小鼠颈淋巴结舌癌转移的疗效。
口腔癌经常转移到邻近的颈部淋巴结(cln),导致全身播散和预后不良。鼻内给药可直接进入颈部淋巴,使局部药物浓度高,同时最大限度地减少全身暴露。本研究评估了两种血管内皮生长因子受体(VEGFR)-3抑制剂——苹果酸西地尼(CDNB)和盐酸帕唑帕尼(PPNB)在舌癌小鼠模型中的药代动力学和抗转移效果。药代动力学分析显示,尽管两种药物的血浆浓度较低,但鼻内给药产生的CLN浓度明显高于静脉给药。在荷瘤小鼠中,与对照组相比,鼻内CDNB显著降低了CLN转移的发生率(0.167)(0.875,p < 0.01),比腹腔内CDNB(0.571)或鼻内PPNB(0.500)更有效。PPNB虽然效力较弱,但显著减少了转移性cln的数量(0.438,p < 0.05)。CDNB表现出更优越和更一致的疗效。PPNB的效果降低可能反映了其较低的剂量(受溶解度限制)和可能的靶标特异性差异。这些发现强调了鼻内给药将VEGFR-3抑制剂递送到cln、抑制淋巴管生成和淋巴转移以及降低全身毒性的潜力。这种方法可能为口腔癌的颈部清扫提供一种非侵入性的替代方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
9.10
自引率
0.00%
发文量
165
审稿时长
2 months
期刊介绍: Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信