Posaconazole loaded Lipid Polymer Hybrid Nanoparticles: Design and Development for Vaginal Drug Delivery

IF 2.7 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Sanjeevani Deshkar, Shubhangi Madankar, Ankita Shinde, Manisha Junnarkar, Avinash Kharat, Roshani Pagar, Ravindra Wavhale, Neelu Nawani
{"title":"Posaconazole loaded Lipid Polymer Hybrid Nanoparticles: Design and Development for Vaginal Drug Delivery","authors":"Sanjeevani Deshkar,&nbsp;Shubhangi Madankar,&nbsp;Ankita Shinde,&nbsp;Manisha Junnarkar,&nbsp;Avinash Kharat,&nbsp;Roshani Pagar,&nbsp;Ravindra Wavhale,&nbsp;Neelu Nawani","doi":"10.1007/s12247-024-09898-8","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The treatment of recurrent vaginal fungal infections by topical application of antifungal agent is limited mainly due to poor solubility and low levels of the drug available at the site of action in the affected tissues. For this reason, research is being done on novel drug-delivery technologies and new therapeutic compounds. Posaconazole (POS) is a broad-spectrum antifungal reported to be effective in managing serious infections and drug-resistant fungal strains.</p><h3>Purpose</h3><p>In the present study, lipid polymer hybrid nanoparticles (LPHNP) were prepared to achieve site-specific targeting and improve tissue uptake of POS. A sustained release profile and higher drug encapsulation are both rendered possible by the structural benefits of polymers and the biomimetic characteristics of lipids.</p><h3>Material and Methods</h3><p>In the present study, LPHNP were prepared using POS, polycaprolactone (PCL), soya lecithin, and polyvinyl alcohol (PVA) as structural constituents by emulsification followed by solvent evaporation. The formulation batches were subsequently optimized using a 3-factor 3-level Box Behnken statistical design. Particle size, zeta potential, surface morphology by transmission electron microscopy (TEM), drug entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), and in vitro drug release were all employed to characterize the formulations. A cell viability assay was used to conduct cytotoxicity studies of the LPHNP on the SiHa cell line. The cellular uptake was assessed using a confocal laser scanning microscope and flow cytometry.</p><h3>Results</h3><p>The particle size, polydispersity index (PDI), and zeta potential of the optimized LPHNP batch were found to be 465 ± 58.13 nm, 0.17 ± 0.07, and -12 mV respectively. The entrapment efficiency was found to be 90.92 ± 0.22%. The antifungal activity of POS-loaded LPHNP was significantly higher than the pure drug. The release of drug from the LPHNP system was observed to be sustained for up to 24 h. The in vitro cell cytotoxicity (MTT assay) and cellular uptake were evaluated using SiHa cell lines. The MTT assay of the developed LPHNP formulation demonstrated negligible cytotoxicity as compared to that of pure POS. The cell uptake studies by flow cytometry showed greater cell internalization of the formulation (58.4% after 4 h incubation) owing to the smaller particle size of the nanoparticles. Similar results (78% after 4 h incubation) were observed in confocal microscopy indicating probable higher therapeutic efficacy for deep-seated fungal infections.</p><h3>Conclusion</h3><p>Conclusively, LPHNP is a promising drug delivery system for vaginal targeting of therapeutic moieties.</p></div>","PeriodicalId":656,"journal":{"name":"Journal of Pharmaceutical Innovation","volume":"20 1","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmaceutical Innovation","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s12247-024-09898-8","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

Background

The treatment of recurrent vaginal fungal infections by topical application of antifungal agent is limited mainly due to poor solubility and low levels of the drug available at the site of action in the affected tissues. For this reason, research is being done on novel drug-delivery technologies and new therapeutic compounds. Posaconazole (POS) is a broad-spectrum antifungal reported to be effective in managing serious infections and drug-resistant fungal strains.

Purpose

In the present study, lipid polymer hybrid nanoparticles (LPHNP) were prepared to achieve site-specific targeting and improve tissue uptake of POS. A sustained release profile and higher drug encapsulation are both rendered possible by the structural benefits of polymers and the biomimetic characteristics of lipids.

Material and Methods

In the present study, LPHNP were prepared using POS, polycaprolactone (PCL), soya lecithin, and polyvinyl alcohol (PVA) as structural constituents by emulsification followed by solvent evaporation. The formulation batches were subsequently optimized using a 3-factor 3-level Box Behnken statistical design. Particle size, zeta potential, surface morphology by transmission electron microscopy (TEM), drug entrapment efficiency, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), and in vitro drug release were all employed to characterize the formulations. A cell viability assay was used to conduct cytotoxicity studies of the LPHNP on the SiHa cell line. The cellular uptake was assessed using a confocal laser scanning microscope and flow cytometry.

Results

The particle size, polydispersity index (PDI), and zeta potential of the optimized LPHNP batch were found to be 465 ± 58.13 nm, 0.17 ± 0.07, and -12 mV respectively. The entrapment efficiency was found to be 90.92 ± 0.22%. The antifungal activity of POS-loaded LPHNP was significantly higher than the pure drug. The release of drug from the LPHNP system was observed to be sustained for up to 24 h. The in vitro cell cytotoxicity (MTT assay) and cellular uptake were evaluated using SiHa cell lines. The MTT assay of the developed LPHNP formulation demonstrated negligible cytotoxicity as compared to that of pure POS. The cell uptake studies by flow cytometry showed greater cell internalization of the formulation (58.4% after 4 h incubation) owing to the smaller particle size of the nanoparticles. Similar results (78% after 4 h incubation) were observed in confocal microscopy indicating probable higher therapeutic efficacy for deep-seated fungal infections.

Conclusion

Conclusively, LPHNP is a promising drug delivery system for vaginal targeting of therapeutic moieties.

泊沙康唑负载的脂质聚合物混合纳米颗粒:阴道给药的设计和开发
背景:局部应用抗真菌药物治疗复发性阴道真菌感染的局限性主要是由于受影响组织中作用部位的药物溶解度差和水平低。因此,人们正在研究新的给药技术和新的治疗化合物。泊沙康唑(Posaconazole, POS)是一种广谱抗真菌药,据报道可有效治疗严重感染和耐药真菌菌株。在本研究中,制备了脂质聚合物混合纳米颗粒(LPHNP),以实现位点特异性靶向并改善POS的组织吸收。聚合物的结构优势和脂质的仿生特性使其具有缓释特性和更高的药物包封性。材料与方法本研究以聚己内酯(PCL)、大豆卵磷脂和聚乙烯醇(PVA)为结构组分,经乳化-溶剂蒸发法制备了LPHNP。随后采用3因素3水平Box Behnken统计设计对制剂批次进行优化。采用粒径、zeta电位、透射电子显微镜(TEM)表面形貌、药物包封效率、傅里叶变换红外光谱(FTIR)、差示扫描量热法(DSC)、x射线衍射(XRD)和体外药物释放等方法对制剂进行表征。采用细胞活力测定法对SiHa细胞系进行了LPHNP的细胞毒性研究。使用共聚焦激光扫描显微镜和流式细胞术评估细胞摄取。结果优化后的LPHNP的粒径为465±58.13 nm, PDI为0.17±0.07,zeta电位为-12 mV。捕集效率为90.92±0.22%。负载poss的LPHNP抗真菌活性明显高于纯药。观察到药物从LPHNP系统的释放持续长达24小时。体外细胞毒性(MTT测定)和细胞摄取使用SiHa细胞系进行评估。MTT试验表明,与纯POS相比,开发的LPHNP制剂的细胞毒性可以忽略不计。流式细胞术的细胞摄取研究显示,由于纳米颗粒尺寸较小,该制剂的细胞内化率更高(孵育4小时后为58.4%)。在共聚焦显微镜下观察到类似的结果(孵育4小时后78%),表明对深部真菌感染可能有更高的治疗效果。结论LPHNP是一种很有前途的阴道靶向给药系统。
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
Journal of Pharmaceutical Innovation
Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-
CiteScore
3.70
自引率
3.80%
发文量
90
审稿时长
>12 weeks
期刊介绍: The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.
×
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