4′-OH as the Action Site of Lipids and MRP1 for Enhanced Transdermal Delivery of Flavonoids

透皮 哈卡特 角质层 渗透 类黄酮 亲脂性 药理学 药物输送 化学 立体化学 生物化学 有机化学 医学 抗氧化剂 体外 病理
作者
Zhuxian Wang,Yi Hu,Yaqi Xue,Yufan Wu,Quanfu Zeng,Hongkai Chen,Yinglin Guo,Peiyi Liang,Liang Tao,Chunyan Shen,Cuiping Jiang,Li Liu,Qun Shen,Hongxia Zhu,Qiang Liu
出处
期刊:ACS Applied Materials & Interfaces [American Chemical Society]
被引量:6
标识
DOI:10.1021/acsami.2c18086
摘要

To date, the transdermal delivery study mainly focused on the drug delivery systems' design and efficacy evaluation. Few studies reported the structure-affinity relationship of the drug with the skin, further revealing the action sites of the drugs for enhanced permeation. Flavonoids attained a considerable interest in transdermal administration. The aim is to develop a systematic approach to evaluate the substructures that were favorable for flavonoid delivery into the skin and understand how these action sites interacted with lipids and bound to multidrug resistance protein 1 (MRP1) for enhanced transdermal delivery. First, we investigated the permeation properties of various flavonoids on the porcine skin or rat skin. We found that 4'-OH (hydroxyl group on the carbon 4' position) rather than 7-OH on the flavonoids was the key group for flavonoid permeation and retention, while 4'-OCH3 and -CH2═CH2-CH-(CH3)2 were unfavorable for drug delivery. 4'-OH could decrease flavonoids' lipophilicity to an appropriate log P and polarizability for better transdermal drug delivery. In the stratum corneum, flavonoids used 4'-OH as a hand to specifically grab the C═O group of the ceramide NS (Cer), which increased the miscibility of flavonoids and Cer and then disturbed the lipid arrangement of Cer, thereby facilitating their penetration. Subsequently, we constructed overexpressed MRP1 HaCaT/MRP1 cells by permanent transfection of human MRP1 cDNA in wild HaCaT cells. In the dermis, we observed that 4'-OH, 7-OH, and 6-OCH3 substructures were involved in H-bond formation within MRP1, which increased the flavonoid affinity with MRP1 and flavonoid efflux transport. Moreover, the expression of MRP1 was significantly enhanced after the treatment of flavonoids on the rat skin. Collectively, 4'-OH served as the action site for increased lipid disruption and enhanced affinity for MRP1, which facilitate the transdermal delivery of flavonoids, providing valuable guidelines for molecular modification and drug design of flavonoids.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
胡须应助祁乐安采纳,获得20
1秒前
刘钱美子完成签到,获得积分10
1秒前
qian完成签到 ,获得积分10
1秒前
李治海发布了新的文献求助10
2秒前
醉眠完成签到 ,获得积分10
2秒前
Fin2046完成签到,获得积分10
2秒前
学不懂数学完成签到,获得积分10
3秒前
莓烦恼完成签到 ,获得积分10
4秒前
5秒前
白江虎完成签到,获得积分10
6秒前
7秒前
阳光的凌雪完成签到 ,获得积分10
8秒前
文艺小馒头完成签到,获得积分10
8秒前
赵赵发布了新的文献求助20
9秒前
橙子发布了新的文献求助10
11秒前
12秒前
Wsyyy完成签到 ,获得积分10
14秒前
14秒前
ganjqly完成签到,获得积分10
14秒前
董惠玲66发布了新的文献求助10
15秒前
g7001完成签到,获得积分10
17秒前
blue发布了新的文献求助10
17秒前
刘铭晨完成签到,获得积分10
17秒前
XYZ完成签到 ,获得积分10
18秒前
wmszhd完成签到,获得积分10
18秒前
付艳完成签到,获得积分10
18秒前
CAOHOU应助论文顺利采纳,获得10
19秒前
nancy93228完成签到 ,获得积分10
20秒前
搜集达人应助JW采纳,获得10
22秒前
???完成签到,获得积分10
24秒前
优秀的白曼完成签到,获得积分10
26秒前
王小西发布了新的文献求助10
27秒前
碧蓝莫言完成签到 ,获得积分10
29秒前
清璃完成签到 ,获得积分10
30秒前
虚心的寒梦完成签到,获得积分10
30秒前
秋秋发布了新的文献求助10
30秒前
kkk完成签到,获得积分10
32秒前
bnhh完成签到,获得积分10
32秒前
Betty应助lindahuang采纳,获得10
33秒前
ilk666完成签到,获得积分10
34秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038303
求助须知:如何正确求助?哪些是违规求助? 3576013
关于积分的说明 11374210
捐赠科研通 3305780
什么是DOI,文献DOI怎么找? 1819322
邀请新用户注册赠送积分活动 892672
科研通“疑难数据库(出版商)”最低求助积分说明 815029