Bioavailability enhancement of formononetin by incorporation of natural bioenhancer in phospholipid complex.

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Arun Agarwal, Shailesh Dadge, Richa Garg, Rakesh Kumar Sharma, Divya Chauhan, Roshan Katekar, Shivam Rathaur, Kalyan Mitra, Jiaur R Gayen
{"title":"Bioavailability enhancement of formononetin by incorporation of natural bioenhancer in phospholipid complex.","authors":"Arun Agarwal, Shailesh Dadge, Richa Garg, Rakesh Kumar Sharma, Divya Chauhan, Roshan Katekar, Shivam Rathaur, Kalyan Mitra, Jiaur R Gayen","doi":"10.1080/10837450.2024.2427838","DOIUrl":null,"url":null,"abstract":"<p><p>Formononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes. Our data showed both groups improved FNT water solubility and oil-water partition coefficient. NMR, DSC, and SEM were performed to identify the interaction and the geometrical nature of complex. When compared, FNT-PIP-PC released more FNT in <i>in vitro</i> release and permeation through Caco-2 monolayer than FNT-PC and pure FNT. <i>In vitro</i> data was consistent with the <i>in vivo</i> pharmacokinetic profile that showed increased, C<sub>max</sub> and AUC<sub>(0-24)</sub> by 7.16 and 23.33-fold and 29.65 and 23.33-fold at 5 and 10 mg/kg in FNT-PIP-PC, compared to pure FNT. Additionally, co-treatment of PIP and FNT improved <i>in vitro</i> pharmacological action in dexamethasone-induced osteoporosis. Thus, our study showed addition of PIP in FNT-PC further increases FNT water solubility and protects it from phase II metabolism, leading to enhanced bioavailability with improved pharmacological activity.</p>","PeriodicalId":20004,"journal":{"name":"Pharmaceutical Development and Technology","volume":" ","pages":"1148-1161"},"PeriodicalIF":2.6000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceutical Development and Technology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/10837450.2024.2427838","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/17 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Formononetin (FNT) has limited application due to poor water solubility and substantial phase II metabolism. In the present study, we used phospholipid complex (PC) containing FNT and UDP-glucuronosyltransferase (UGT1A1) inhibitor piperine (PIP) to overcome FNT limitations. We characterized and compared both FNT-PC and FNT-PIP-PC complexes. Our data showed both groups improved FNT water solubility and oil-water partition coefficient. NMR, DSC, and SEM were performed to identify the interaction and the geometrical nature of complex. When compared, FNT-PIP-PC released more FNT in in vitro release and permeation through Caco-2 monolayer than FNT-PC and pure FNT. In vitro data was consistent with the in vivo pharmacokinetic profile that showed increased, Cmax and AUC(0-24) by 7.16 and 23.33-fold and 29.65 and 23.33-fold at 5 and 10 mg/kg in FNT-PIP-PC, compared to pure FNT. Additionally, co-treatment of PIP and FNT improved in vitro pharmacological action in dexamethasone-induced osteoporosis. Thus, our study showed addition of PIP in FNT-PC further increases FNT water solubility and protects it from phase II metabolism, leading to enhanced bioavailability with improved pharmacological activity.

通过在磷脂复合物中加入天然生物增强剂提高福莫西汀的生物利用率
福莫西汀(FNT)由于水溶性差和大量 II 期代谢,其应用受到限制。在本研究中,我们使用含有 FNT 和 UDP-葡萄糖醛酸转移酶(UGT1A1)抑制剂哌啶(PIP)的磷脂复合物(PC)来克服 FNT 的局限性。我们对 FNT-PC 和 FNT-PIP-PC 复合物进行了表征和比较。数据显示,两组复合物都提高了 FNT 的水溶性和油水分配系数。通过核磁共振、DSC 和扫描电子显微镜鉴定了复合物的相互作用和几何性质。与纯 FNT 相比,FNT-PIP-PC 在体外释放和 Caco-2 单层渗透中释放的 FNT 更多。体外数据与体内药代动力学特征一致,显示与纯 FNT 相比,FNT-PIP-PC 在 5 和 10 mg/kg 时的 Cmax 和 AUC(0-24)分别增加了 7.16 倍和 23.33 倍,以及 29.65 倍和 23.33 倍。此外,在地塞米松诱导的骨质疏松症的体外药理作用中,PIP 和 FNT 的联合处理也有所改善。因此,我们的研究表明,在 FNT-PC 中添加 PIP 可进一步提高 FNT 的水溶性,并保护其免受 II 期代谢的影响,从而提高生物利用度,改善药理活性。
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
5.90
自引率
2.90%
发文量
82
审稿时长
1 months
期刊介绍: Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology. Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as: -Preformulation and pharmaceutical formulation studies -Pharmaceutical materials selection and characterization -Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation -QbD in the form a risk assessment and DoE driven approaches -Design of dosage forms and drug delivery systems -Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies -Drug delivery systems research and quality improvement -Pharmaceutical regulatory affairs This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.
×
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