Myristic Acid Solid Lipid Nanoparticles Enhance the Oral Bioavailability and Therapeutic Efficacy of Rifaximin against MRSA Pneumonia.

Yumin Zhang, Aoxue Zhang, Dongmei Chen, Shuyu Xie
{"title":"Myristic Acid Solid Lipid Nanoparticles Enhance the Oral Bioavailability and Therapeutic Efficacy of Rifaximin against MRSA Pneumonia.","authors":"Yumin Zhang, Aoxue Zhang, Dongmei Chen, Shuyu Xie","doi":"10.2174/0115672018276382231207103955","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption. Solid lipid nanoparticles have good biocompatibility, high drug loading, sustained release performance, and the inertia of lipids in gastric acid, which facilitates oral drug delivery.</p><p><strong>Objective: </strong>In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs).</p><p><strong>Methods: </strong>This study first prepared RFX-SLNs through hot melt emulsification and ultrasonic methods and selected the optimal formula of RFX-SLNs through single-factor screening. Afterward, the particle size, zeta potential, and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high-performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model.</p><p><strong>Results: </strong>The optimal formulation of RFX-SLNs was 1% RFX with water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical in shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. This indicates that RFX-SLNs can be used for the oral treatment of bacterial infections. Compared to RFX, RFX-SLNs showed good therapeutic effects in a mouse MRSA pneumonia infection model.</p><p><strong>Conclusion: </strong>This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs. This not only opens up avenues for the clinical application of RFX but also provides a way for the development of new dosage forms of water-soluble drugs and the expansion of their clinical application scope.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current drug delivery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115672018276382231207103955","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption. Solid lipid nanoparticles have good biocompatibility, high drug loading, sustained release performance, and the inertia of lipids in gastric acid, which facilitates oral drug delivery.

Objective: In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs).

Methods: This study first prepared RFX-SLNs through hot melt emulsification and ultrasonic methods and selected the optimal formula of RFX-SLNs through single-factor screening. Afterward, the particle size, zeta potential, and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high-performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model.

Results: The optimal formulation of RFX-SLNs was 1% RFX with water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical in shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. This indicates that RFX-SLNs can be used for the oral treatment of bacterial infections. Compared to RFX, RFX-SLNs showed good therapeutic effects in a mouse MRSA pneumonia infection model.

Conclusion: This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs. This not only opens up avenues for the clinical application of RFX but also provides a way for the development of new dosage forms of water-soluble drugs and the expansion of their clinical application scope.

肉豆蔻酸固体脂质纳米颗粒提高利福昔明的口服生物利用度和对 MRSA 肺炎的疗效
背景:耐甲氧西林金黄色葡萄球菌(MRSA)肺炎是导致死亡的主要原因之一,也给医疗系统造成了巨大的经济负担。利福昔明(Rifaximin,RFX)对 MRSA 具有良好的抗菌活性,但由于口服吸收不良,其临床应用受到限制。固体脂质纳米颗粒具有良好的生物相容性、高载药量、持续释放性能以及脂质在胃酸中的惰性,有利于口服给药:为了提高利福昔明的口服生物利用度,扩大RFX治疗MRSA肺炎的临床应用,本研究开发了RFX载药肉豆蔻酸固体脂质纳米颗粒(RFX-SLNs):本研究首先通过热熔乳化法和超声波法制备了RFX-SLNs,并通过单因素筛选选出了RFX-SLNs的最佳配方。然后测定了RFX-SLNs的粒径、ZETA电位和多分散指数(PDI),用透射电子显微镜观察了RFX-SLNs的形态,并用高效液相色谱法检测了RFX-SLNs的包封效率(EE)和载药量(LC)。然后,通过体外释放和药代动力学研究了 RFX-SLNs 的缓释能力和口服生物利用度。最后,利用小鼠 MRSA 肺炎感染模型研究了 RFX-SLNs 对 MRSA 肺炎感染的治疗效果:结果:RFX-SLNs 的最佳配方为 1%的 RFX,水(3% PVA)和油(肉豆蔻酸)的比例为 1:19。RFX-SLNs 呈球形,表面光滑,大小均匀。三个不同批次的 RFX-SLNs 的 EE 和 LC 分别为 89.35±2.47%、90.45±3.69%、88.72±1.18% 和 9.50±0.01%、10.09±0.01% 和 9.68±0.00%。体外释放和药代动力学研究表明,肉豆蔻酸固体脂质纳米颗粒如预期的那样表现出良好的持续释放性,并使 RFX 的口服生物利用度提高了 2.18 倍。这表明 RFX-SLNs 可用于细菌感染的口服治疗。与 RFX 相比,RFX-SLNs 在小鼠 MRSA 肺炎感染模型中显示出良好的治疗效果:本研究表明,肉豆蔻酸固体脂质纳米颗粒可能是增强 RFX 和其他不溶性药物口服吸收和治疗效果的有效方法。这不仅为 RFX 的临床应用开辟了道路,也为开发水溶性药物的新剂型和扩大其临床应用范围提供了途径。
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
自引率
0.00%
发文量
0
×
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