Amphiphilic Cyclodextrin Nanoparticles as Delivery System for Idebenone: A Preformulation Study

Author:

De Gaetano Federica1,Scala Angela1ORCID,Celesti Consuelo23ORCID,Lambertsen Larsen Kim4ORCID,Genovese Fabio5ORCID,Bongiorno Corrado6ORCID,Leggio Loredana7ORCID,Iraci Nunzio7ORCID,Iraci Nunzio1ORCID,Mazzaglia Antonino8ORCID,Ventura Cinzia Anna1

Affiliation:

1. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno d’Alcontres 31, 98166 Messina, Italy

2. Department of Engineering, University of Messina, Contrada Di Dio, 98166 Messina, Italy

3. Department of Clinical and Experimental Medicine, University of Messina, Via Consolare Valeria, 98125 Messina, Italy

4. Department of Chemistry and Bioscience, Aalborg University, Frederik Bajers Vej 7H, 9220 Aalborg, Denmark

5. Technical, Economic and Technological Institute “Girolamo Caruso”, Via John Fitzgerald Kennedy 2, 91011 Alcamo, Italy

6. National Council of Research, Institute of Microelectronics and Microsystems (CNR-IMM), Strada VIII n. 5-Zona Industriale, 95121 Catania, Italy

7. Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, Torre Biologica, Via Santa Sofia 97, 95125 Catania, Italy

8. National Council of Research, Institute for the Study of Nanostructured Materials (CNR-ISMN), URT of Messina c/o Department of Chemical, Biological, Pharmaceutical and Environmental Sciences of the University of Messina, V.le F. Stagno d’Alcontres 31, 98166 Messina, Italy

Abstract

Idebenone (IDE), a synthetic short-chain analogue of coenzyme Q10, is a potent antioxidant able to prevent lipid peroxidation and stimulate nerve growth factor. Due to these properties, IDE could potentially be active towards cerebral disorders, but its poor water solubility limits its clinical application. Octanoyl-β-cyclodextrin is an amphiphilic cyclodextrin (ACyD8) bearing, on average, ten octanoyl substituents able to self-assemble in aqueous solutions, forming various typologies of supramolecular nanoassemblies. Here, we developed nanoparticles based on ACyD8 (ACyD8-NPs) for the potential intranasal administration of IDE to treat neurological disorders, such as Alzheimer’s Disease. Nanoparticles were prepared using the nanoprecipitation method and were characterized for their size, zeta potential and morphology. STEM images showed spherical particles, with smooth surfaces and sizes of about 100 nm, suitable for the proposed therapeutical aim. The ACyD8-NPs effectively loaded IDE, showing a high encapsulation efficiency and drug loading percentage. To evaluate the host/guest interaction, UV-vis titration, mono- and two-dimensional NMR analyses, and molecular modeling studies were performed. IDE showed a high affinity for the ACyD8 cavity, forming a 1:1 inclusion complex with a high association constant. A biphasic and sustained release of IDE was observed from the ACyD8-NPs, and, after a burst effect of about 40%, the release was prolonged over 10 days. In vitro studies confirmed the lack of toxicity of the IDE/ACyD8-NPs on neuronal SH-SY5Y cells, and they demonstrated their antioxidant effect upon H2O2 exposure, as a general source of ROS.

Publisher

MDPI AG

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.7亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2025 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3