Formulation, optimization and evaluation of ocular gel containing nebivolol Hcl-loaded ultradeformable spanlastics nanovesicles: In vitro and in vivo studies

IF 5.2 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Mohamed Yasser , Eman E. El Naggar , Nehal Elfar , Mahmoud H. Teaima , Mohamed A. El-Nabarawi , Sammar Fathy Elhabal
{"title":"Formulation, optimization and evaluation of ocular gel containing nebivolol Hcl-loaded ultradeformable spanlastics nanovesicles: In vitro and in vivo studies","authors":"Mohamed Yasser ,&nbsp;Eman E. El Naggar ,&nbsp;Nehal Elfar ,&nbsp;Mahmoud H. Teaima ,&nbsp;Mohamed A. El-Nabarawi ,&nbsp;Sammar Fathy Elhabal","doi":"10.1016/j.ijpx.2023.100228","DOIUrl":null,"url":null,"abstract":"<div><p>The study aims to improve the ocular delivery of Nebivolol HCL (NBV) belonging to the Biopharmaceutics classification system (BCSII) by using spanlastic nanovesicles (SNVs) for ophthalmic delivery and incorporating them into hydroxypropyl methylcellulose gel with ketorolac tromethamine (KET) as an anti-inflammatory to improve glaucoma complications like Conjunctivitis. SNVs were prepared by ethanol injection technique using span (60) as a surfactant and labrasol as an edge activator (EA). The impact of formulation factors on SNVs properties was investigated using a Box-Behnken design. In vitro evaluations showed that the formulations (F1, F4, and F14), containing Span 60 and labrasol as EA (25%, 50%, and 25%), exhibited high EE% with low PS and high ZP and DI. Additionally, 61.72 ± 0.77%, 58.97 ± 1.44%, and 56.20 ± 2.32% of the NBV amount were released from F1, F4, and F14 after 5 h, compared to 93.94 ± 1.21% released from drug suspension. The selected formula (G1), containing F1 in combination with KET and 2% <em>w</em>/w HPMC, exhibited 76.36 ± 0.90% drug release after 12 h. Ex vivo Confocal laser scanning revealed a high penetration of NBV-SNVs gel that ascertained the results of the in-vitro <em>study</em>. In vivo studies showed a significant decrease in glaucoma compared to drug suspension, and histopathological studies showed improvement in glaucomatous eye retinal atrophy. G1 is considered a promising approach to improving ocular permeability, absorption, and anti-inflammatory activity, providing a safer alternative to current regimens.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"7 ","pages":"Article 100228"},"PeriodicalIF":5.2000,"publicationDate":"2024-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590156723000725/pdfft?md5=b2ff799666c90e95ea2c791759c45b4b&pid=1-s2.0-S2590156723000725-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics: X","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590156723000725","RegionNum":2,"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 study aims to improve the ocular delivery of Nebivolol HCL (NBV) belonging to the Biopharmaceutics classification system (BCSII) by using spanlastic nanovesicles (SNVs) for ophthalmic delivery and incorporating them into hydroxypropyl methylcellulose gel with ketorolac tromethamine (KET) as an anti-inflammatory to improve glaucoma complications like Conjunctivitis. SNVs were prepared by ethanol injection technique using span (60) as a surfactant and labrasol as an edge activator (EA). The impact of formulation factors on SNVs properties was investigated using a Box-Behnken design. In vitro evaluations showed that the formulations (F1, F4, and F14), containing Span 60 and labrasol as EA (25%, 50%, and 25%), exhibited high EE% with low PS and high ZP and DI. Additionally, 61.72 ± 0.77%, 58.97 ± 1.44%, and 56.20 ± 2.32% of the NBV amount were released from F1, F4, and F14 after 5 h, compared to 93.94 ± 1.21% released from drug suspension. The selected formula (G1), containing F1 in combination with KET and 2% w/w HPMC, exhibited 76.36 ± 0.90% drug release after 12 h. Ex vivo Confocal laser scanning revealed a high penetration of NBV-SNVs gel that ascertained the results of the in-vitro study. In vivo studies showed a significant decrease in glaucoma compared to drug suspension, and histopathological studies showed improvement in glaucomatous eye retinal atrophy. G1 is considered a promising approach to improving ocular permeability, absorption, and anti-inflammatory activity, providing a safer alternative to current regimens.

Abstract Image

含有盐酸奈必洛尔的超可塑spanlastics纳米颗粒的眼用凝胶的配制、优化和评估:体外和体内研究
这项研究的目的是通过使用spanlastic纳米颗粒(SNVs)进行眼部给药,并将其加入羟丙基甲基纤维素凝胶和作为消炎药的酮咯酸氨基丁三醇(KET)中,改善属于生物制药分类系统(BCSII)的奈必洛尔盐酸盐(NBV)的眼部给药,以改善结膜炎等青光眼并发症。SNV 采用乙醇注射技术制备,使用 span (60) 作为表面活性剂,labrasol 作为边缘活化剂 (EA)。采用方框-贝肯设计法研究了制剂因素对SNV特性的影响。体外评估结果表明,含有司盘 60 和拉布拉索尔作为 EA(25%、50% 和 25%)的配方(F1、F4 和 F14)表现出高 EE%、低 PS、高 ZP 和 DI。此外,5 小时后,F1、F4 和 F14 释放的 NBV 量分别为 61.72 ± 0.77%、58.97 ± 1.44% 和 56.20 ± 2.32%,而药物悬浮液释放的 NBV 量为 93.94 ± 1.21%。所选配方(G1)含有 F1 与 KET 和 2% w/w HPMC,12 小时后药物释放率为 76.36 ± 0.90%。体内激光共聚焦扫描显示,NBV-SNVs 凝胶的渗透率很高,证实了体外研究的结果。体内研究显示,与药物混悬液相比,青光眼的发病率明显降低,组织病理学研究显示,青光眼眼视网膜萎缩的情况有所改善。G1 被认为是一种有希望改善眼部渗透性、吸收性和抗炎活性的方法,为目前的治疗方案提供了一种更安全的替代方案。
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
International Journal of Pharmaceutics: X
International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
6.60
自引率
0.00%
发文量
32
审稿时长
24 days
期刊介绍: International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible. International Journal of Pharmaceutics: X authors will pay an article publishing charge (APC), have a choice of license options, and retain copyright. Please check the APC here. The journal is indexed in SCOPUS, PUBMED, PMC and DOAJ. The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.
×
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