Design and therapeutic application of trans‐sodium crocetinate‐loaded cyclodextrin metal–organic frameworks as an enteric preparation for treating chronic heart failure

化学 环糊精 肠衣 金属有机骨架 有机化学 色谱法 吸附
作者
Renqiang Ma,X. Chen,Tao Hu,Fang-Ke Huang,X. L. Li,Xianmin Huang,Bao He,Liwen Feng,Junping Kou,Boyang Yu
出处
期刊:Applied Organometallic Chemistry [Wiley]
标识
DOI:10.1002/aoc.7411
摘要

Chronic heart failure (CHF) arises from structural and functional changes in the myocardial tissue attributable to various etiologies. Crocetin and its derivative trans‐sodium crocetinate (TSC) have exhibited cardioprotective attributes; however, their poor aqueous solubility and bioavailability impede clinical development. This study aimed to construct a cyclodextrin metal–organic frameworks (CDMOFs)‐based oral delivery system to enhance the pharmacokinetic profile and therapeutic efficacy of TSC for CHF treatment. TSC was loaded into the synthesized γ‐CDMOFs via vacuum adsorption. The CDMOFs@TSC formulation was characterized and evaluated in vitro. Pharmacokinetic and pharmacodynamic analyses were performed in beagle dogs and CHF rats induced by coronary artery ligation, respectively. Both TSC and CDMOFs@TSC elicited no discernible toxicity or pathological changes in major organs of rats, providing preliminary evidence for their biosafety. Pharmacokinetic study in beagle dogs demonstrated that CDMOFs@TSC capsules markedly increase the relative oral bioavailability by 198% versus free TSC capsules. In rats afflicted with CHF, the administration of CDMOFs@TSC yielded notable enhancements in cardiac function. Additionally, it precipitated a reduction in biomarkers linked to myocardial injury, manifested anti‐inflammatory and antifibrotic effects, and induced alterations in myocardial energy metabolism. This is the first report of CDMOFs‐based oral delivery to improve the TSC bioavailability and efficacy. The utilization of CDMOFs@TSC resulted in superior therapeutic outcomes in comparison to standalone TSC by optimizing pharmacokinetics and precise targeted delivery. These results highlight the clinical potential of CDMOF as porous carriers to enable oral delivery of natural products for CHF therapy.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
刚刚
刚刚
wzppp发布了新的文献求助10
1秒前
1秒前
2秒前
2秒前
3秒前
哈哈哈完成签到,获得积分10
3秒前
唐唐完成签到 ,获得积分10
3秒前
醉熏的初柳完成签到,获得积分10
4秒前
6秒前
六碗饭发布了新的文献求助10
6秒前
xll完成签到,获得积分10
7秒前
小云完成签到 ,获得积分10
7秒前
爱笑鸡翅发布了新的文献求助10
8秒前
8秒前
丘比特应助乐观明雪采纳,获得10
9秒前
拉布拉卡发布了新的文献求助10
9秒前
英姑应助逆天而行采纳,获得10
9秒前
万能图书馆应助勤恳的鸿采纳,获得10
9秒前
爆米花应助LOT采纳,获得10
9秒前
9秒前
11秒前
12秒前
12秒前
12秒前
严永桂完成签到,获得积分20
13秒前
英姑应助小北采纳,获得10
14秒前
复杂的溪流完成签到,获得积分10
14秒前
李健应助拉布拉卡采纳,获得10
14秒前
HelenZ完成签到,获得积分10
14秒前
乐观明雪完成签到,获得积分20
14秒前
冬~发布了新的文献求助10
14秒前
billionbewater完成签到 ,获得积分10
16秒前
香蕉觅云应助crush_zyd采纳,获得10
16秒前
Hymer发布了新的文献求助10
16秒前
sisisij发布了新的文献求助10
16秒前
Green完成签到,获得积分10
17秒前
VDC发布了新的文献求助10
17秒前
克丽完成签到 ,获得积分10
18秒前
高分求助中
Evolution 10000
Becoming: An Introduction to Jung's Concept of Individuation 600
Distribution Dependent Stochastic Differential Equations 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
The Kinetic Nitration and Basicity of 1,2,4-Triazol-5-ones 440
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3159243
求助须知:如何正确求助?哪些是违规求助? 2810372
关于积分的说明 7887509
捐赠科研通 2469200
什么是DOI,文献DOI怎么找? 1314702
科研通“疑难数据库(出版商)”最低求助积分说明 630697
版权声明 602012