Novel mucoadhesive lysine based glycated self-nanoemulsifying drug delivery system for targeted delivery against respiratory infection

IF 4.9 3区 医学 Q1 PHARMACOLOGY & PHARMACY
Iqra Khan , Rabia Arshad , Waqar Aman , Kashif Barkat , Abdul Malik , Tanveer A. Tabish , Nikhat J. Siddiqi
{"title":"Novel mucoadhesive lysine based glycated self-nanoemulsifying drug delivery system for targeted delivery against respiratory infection","authors":"Iqra Khan ,&nbsp;Rabia Arshad ,&nbsp;Waqar Aman ,&nbsp;Kashif Barkat ,&nbsp;Abdul Malik ,&nbsp;Tanveer A. Tabish ,&nbsp;Nikhat J. Siddiqi","doi":"10.1016/j.jddst.2025.107574","DOIUrl":null,"url":null,"abstract":"<div><div>The aim of this study was to improve the therapeutic efficacy, drug delivery and physicochemical features of antimicrobial peptides (AMPs) L-Lysine, for chronic obstructive pulmonary disease (COPD) by developing a glycosylated self-nanoemulsifying drug delivery system (SNEDDS). Roflumilast (Rof) a phosphodiesterase 4 (PDE4) inhibitor, was entrapped within the SNEDDS system (Glucolysinated Rof SNEDDS) for targeted COPD treatment. The Glucolysinated Rof SNEDDS were successfully formulated and characterized in terms of physicochemical properties, in vitro as well as in vivo efficacy. Conjugation chemistry was confirmed using FTIR spectroscopy, mean droplet size of SNEDDS was 222 ± 0.46 nm, with 0.42 ± 0.11 PDI and −24.3 ± 1.20 mV zeta potential. The formulation demonstrated outstanding mucoadhesion capabilities, with a 95 % improvement in drug entrapment efficiency and 80 % sustained drug release over 12 h. Toxicity assessments were conducted by Pharmacokinetics approaches, which confirmed the formulation's safety. Strong antibacterial action was revealed against <em>Pseudomonas aeruginosa</em>, which disrupt bacterial membrane integrity as demonstrated with SEM imaging. PDE4 inhibition was confirmed by strong binding energy in docking analysis. Serum biochemistry analysis remained constant throughout treatment, and histopathological investigations indicated the shielding effect of excipients used. These results presented, highlight the potential of Glucolysinated Rof SNEDDS as a novel and effective drug delivery system for targeted COPD therapy, synergizing therapeutic efficacy with biocompatibility.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"114 ","pages":"Article 107574"},"PeriodicalIF":4.9000,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Delivery Science and Technology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1773224725009773","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

The aim of this study was to improve the therapeutic efficacy, drug delivery and physicochemical features of antimicrobial peptides (AMPs) L-Lysine, for chronic obstructive pulmonary disease (COPD) by developing a glycosylated self-nanoemulsifying drug delivery system (SNEDDS). Roflumilast (Rof) a phosphodiesterase 4 (PDE4) inhibitor, was entrapped within the SNEDDS system (Glucolysinated Rof SNEDDS) for targeted COPD treatment. The Glucolysinated Rof SNEDDS were successfully formulated and characterized in terms of physicochemical properties, in vitro as well as in vivo efficacy. Conjugation chemistry was confirmed using FTIR spectroscopy, mean droplet size of SNEDDS was 222 ± 0.46 nm, with 0.42 ± 0.11 PDI and −24.3 ± 1.20 mV zeta potential. The formulation demonstrated outstanding mucoadhesion capabilities, with a 95 % improvement in drug entrapment efficiency and 80 % sustained drug release over 12 h. Toxicity assessments were conducted by Pharmacokinetics approaches, which confirmed the formulation's safety. Strong antibacterial action was revealed against Pseudomonas aeruginosa, which disrupt bacterial membrane integrity as demonstrated with SEM imaging. PDE4 inhibition was confirmed by strong binding energy in docking analysis. Serum biochemistry analysis remained constant throughout treatment, and histopathological investigations indicated the shielding effect of excipients used. These results presented, highlight the potential of Glucolysinated Rof SNEDDS as a novel and effective drug delivery system for targeted COPD therapy, synergizing therapeutic efficacy with biocompatibility.

Abstract Image

新型黏附赖氨酸糖化自纳米乳化给药系统用于呼吸道感染的靶向给药
本研究的目的是通过开发糖基化自纳米乳化给药系统(SNEDDS),提高抗菌肽(AMPs) l -赖氨酸对慢性阻塞性肺疾病(COPD)的治疗效果、药物传递和理化特性。罗氟米司特(Roflumilast, Rof)是一种磷酸二酯酶4 (PDE4)抑制剂,被包裹在SNEDDS系统中用于靶向COPD治疗。成功地制备了葡萄糖水解Rof SNEDDS,并对其理化性质、体外和体内药效进行了表征。通过FTIR光谱验证了sndds的偶联化学性质,其平均液滴尺寸为222±0.46 nm, PDI为0.42±0.11,zeta电位为- 24.3±1.20 mV。该制剂表现出优异的黏附能力,药物包载效率提高95%,12 h内药物持续释放率提高80%。通过药代动力学方法进行毒性评估,证实了该制剂的安全性。对铜绿假单胞菌具有较强的抗菌作用,其破坏细菌膜的完整性。在对接分析中通过强结合能证实PDE4的抑制作用。在整个治疗过程中,血清生化分析保持不变,组织病理学调查表明所使用的辅料具有屏蔽作用。这些结果强调了糖水解Rof SNEDDS作为靶向COPD治疗的一种新型有效的药物传递系统的潜力,可以协同治疗疗效和生物相容性。
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
8.00
自引率
8.00%
发文量
879
审稿时长
94 days
期刊介绍: The Journal of Drug Delivery Science and Technology is an international journal devoted to drug delivery and pharmaceutical technology. The journal covers all innovative aspects of all pharmaceutical dosage forms and the most advanced research on controlled release, bioavailability and drug absorption, nanomedicines, gene delivery, tissue engineering, etc. Hot topics, related to manufacturing processes and quality control, are also welcomed.
×
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:604180095
Book学术官方微信