设计创新型纳米载体,提高新型 5-HT6 受体拮抗剂的脑渗透性

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
María Javiera Alvarez-Figueroa , Francisco Nuñez-Navarro , Gonzalo Recabarren-Gajardo , José Vicente González-Aramundiz
{"title":"设计创新型纳米载体,提高新型 5-HT6 受体拮抗剂的脑渗透性","authors":"María Javiera Alvarez-Figueroa ,&nbsp;Francisco Nuñez-Navarro ,&nbsp;Gonzalo Recabarren-Gajardo ,&nbsp;José Vicente González-Aramundiz","doi":"10.1016/j.ijpx.2024.100296","DOIUrl":null,"url":null,"abstract":"<div><div>An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT<sub>6</sub> receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic <em>N</em>-arylsulfonylindole that has demonstrated potent 5-HT<sub>6</sub> receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI&lt;0.2), a negative Z potential (−17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, <em>in vitro</em> studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10<sup>−8</sup> cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist\",\"authors\":\"María Javiera Alvarez-Figueroa ,&nbsp;Francisco Nuñez-Navarro ,&nbsp;Gonzalo Recabarren-Gajardo ,&nbsp;José Vicente González-Aramundiz\",\"doi\":\"10.1016/j.ijpx.2024.100296\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT<sub>6</sub> receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic <em>N</em>-arylsulfonylindole that has demonstrated potent 5-HT<sub>6</sub> receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI&lt;0.2), a negative Z potential (−17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, <em>in vitro</em> studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10<sup>−8</sup> cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.</div></div>\",\"PeriodicalId\":14280,\"journal\":{\"name\":\"International Journal of Pharmaceutics: X\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Pharmaceutics: X\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590156724000689\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics: X","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590156724000689","RegionNum":2,"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

摘要

我们设计了一种基于脂质纳米囊(LNC)的创新纳米载体,以促进新型 5-HT6 受体拮抗剂 PUC-10 通过血脑屏障。PUC-10 是一种新合成的 N-芳基磺酰基吲哚类药物,具有强效的 5-HT6 受体拮抗剂活性,但在水中的溶解度较低,这表明其吸收能力有限。所设计的脂质纳米胶囊具有纳米级尺寸(53 纳米)、单模分布(PI<0.2)、负 Z 电位(-17 ± 7 mV),可有效封装 PUC-10(74%)。此外,LNC 在 4 °C(储存条件)下至少稳定 4 周,在 pH 值为 7.4 的 DMEM 中至少稳定 4 小时,在含有 5 % DMSO 的水中稳定 18 小时,后两种条件均保持在 37 °C。他们还证明,在研究的不同浓度下,细胞活力均未受到影响。最后,模拟血脑屏障(PAMPA-BBB)的体外研究表明,PUC-10 的纳米包囊促进了其在血脑屏障中的渗透,计算出的渗透率为 1.3 × 10-8 厘米/秒,而非纳米包囊的 PUC-10 的渗透率为零。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist

Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist
An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT6 receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic N-arylsulfonylindole that has demonstrated potent 5-HT6 receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI<0.2), a negative Z potential (−17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, in vitro studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10−8 cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
×
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:481959085
Book学术官方微信