Formononetin-Loaded Self-Microemulsion Drug Delivery Systems for Improved Solubility and Oral Bioavailability: Fabrication, Characterization, In Vitro and In Vivo Evaluation

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2024-11-01 DOI:10.1208/s12249-024-02975-8

Zhihui Zou, Yuanyuan Xue, Michael Adu-Frimpong, ChengWei Wang, Zhou Jin, Ying Xu, Jiangnan Yu, Ximing Xu, Yuan Zhu

{"title":"Formononetin-Loaded Self-Microemulsion Drug Delivery Systems for Improved Solubility and Oral Bioavailability: Fabrication, Characterization, In Vitro and In Vivo Evaluation","authors":"Zhihui Zou, Yuanyuan Xue, Michael Adu-Frimpong, ChengWei Wang, Zhou Jin, Ying Xu, Jiangnan Yu, Ximing Xu, Yuan Zhu","doi":"10.1208/s12249-024-02975-8","DOIUrl":null,"url":null,"abstract":"<div><p>This study aimed to construct a self-microemulsion drug delivery system (SMEDDS) for Formononetin (FMN) to improve its solubility and bioavailability while combining the nanocrystals (NCs) technology. The SMEDDS prescription composition was optimized with a pseudo-three-phase diagram, followed by a series of <i>in vitro</i> and <i>in vivo</i> evaluations of the selected optimal prescriptions. FMN-NCs loaded SMEDDS showed a homogeneous spherical shape in the Transmission electron microscope and the particle size was measured as (20.65 ± 1.42) nm. The <i>in vitro</i> cumulative release rate in each dissolution medium within 30 min was higher than 80%, much higher than that of FMN (6%) and FMN-NCs (40%); Cellular experiments confirm that the formulation has a high safety profile and significantly promotes cellular uptake. The results of pharmacokinetics and intestinal absorption in rats showed that the relative bioavailability of FMN-NCs and FMN-NCs loaded SMEDDS were (154.80 ± 3.76)% and (557.73 ± 32.88)%, respectively, and both of them significantly increased the rate and extent of absorption of the drug in intestinal segments. FMN-NCs loaded SMEDDS significantly enhanced the solubility and bioavailability of FMN.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":6925,"journal":{"name":"AAPS PharmSciTech","volume":"25 8","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AAPS PharmSciTech","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1208/s12249-024-02975-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

This study aimed to construct a self-microemulsion drug delivery system (SMEDDS) for Formononetin (FMN) to improve its solubility and bioavailability while combining the nanocrystals (NCs) technology. The SMEDDS prescription composition was optimized with a pseudo-three-phase diagram, followed by a series of in vitro and in vivo evaluations of the selected optimal prescriptions. FMN-NCs loaded SMEDDS showed a homogeneous spherical shape in the Transmission electron microscope and the particle size was measured as (20.65 ± 1.42) nm. The in vitro cumulative release rate in each dissolution medium within 30 min was higher than 80%, much higher than that of FMN (6%) and FMN-NCs (40%); Cellular experiments confirm that the formulation has a high safety profile and significantly promotes cellular uptake. The results of pharmacokinetics and intestinal absorption in rats showed that the relative bioavailability of FMN-NCs and FMN-NCs loaded SMEDDS were (154.80 ± 3.76)% and (557.73 ± 32.88)%, respectively, and both of them significantly increased the rate and extent of absorption of the drug in intestinal segments. FMN-NCs loaded SMEDDS significantly enhanced the solubility and bioavailability of FMN.

Graphical Abstract

Abstract Image

查看原文本刊更多论文

提高溶解度和口服生物利用度的福莫西汀负载型自微乳化给药系统：制造、表征、体外和体内评估。

本研究旨在构建福莫西汀（FMN）的自微乳给药系统（SMEDDS），以提高其溶解度和生物利用度，同时结合纳米晶体（NCs）技术。通过伪三相图优化了 SMEDDS 的处方组成，随后对选定的最佳处方进行了一系列体外和体内评估。在透射电子显微镜下，负载 FMN-NCs 的 SMEDDS 呈均匀球形，粒径为（20.65 ± 1.42）纳米。30分钟内在各溶解介质中的体外累积释放率均高于80%，远高于FMN（6%）和FMN-NCs（40%）；细胞实验证实该制剂具有较高的安全性，并能显著促进细胞吸收。大鼠的药代动力学和肠道吸收结果表明，FMN-NCs 和 FMN-NCs 负载 SMEDDS 的相对生物利用度分别为（154.80 ± 3.76）% 和（557.73 ± 32.88）%，两者都能显著提高药物在肠段的吸收率和吸收程度。FMN-NCs 负载 SMEDDS 能显著提高 FMN 的溶解度和生物利用度。

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

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.