Eduardo José Barbosa, Claudio Fukumori, Sarah de Araújo Sprengel, Thayná Lopes Barreto, Kelly Ishida, Gabriel Lima Barros de Araujo, Nádia Araci Bou-Chacra, Luciana Biagini Lopes
{"title":"Niclosamide nanoemulsion for colorectal cancer: development, physicochemical characterization, and in vitro anticancer activity","authors":"Eduardo José Barbosa, Claudio Fukumori, Sarah de Araújo Sprengel, Thayná Lopes Barreto, Kelly Ishida, Gabriel Lima Barros de Araujo, Nádia Araci Bou-Chacra, Luciana Biagini Lopes","doi":"10.1007/s11051-024-06126-9","DOIUrl":null,"url":null,"abstract":"<div><p>The BCS class II (Biopharmaceutical Classification System) niclosamide has shown promising anticancer activity for colorectal cancer. However, its low water solubility compromises its oral absorption and systemic action. Incorporating niclosamide in nanoemulsion allows to optimize its cell uptake and tumor penetration. This study aimed at the development, physicochemical characterization, and in vitro anticancer activity of a niclosamide nanoemulsion, with HCT-116 as the cell model. Medium- and long-chain lipids were tested to prepare the nanoemulsions, obtained by high-pressure homogenization. Design of experiments was used to optimize the formulations, which were subjected to a stability study at 30 °C/75% relative humidity (RH) and 4 °C. Nanoemulsion efficacy was evaluated in an HCT-116 viability assay and 3D cell culture model. Medium-chain lipids provided better solubility results than long-chain. Miglyol® 812 and poloxamer 188 proved to be suitable components for the system. Niclosamide nanoemulsion (~ 200 nm) was stable for 56 days, presenting monomodal particle size distribution. The cell viability assay with HCT-116 cell line demonstrated that niclosamide cytoxicity was both time and concentration dependent. In the 3D cell culture model, size and zeta potential may have influenced drug penetration in the spheroid. Incorporating the drug substance in a nanostructured system was pivotal to potentiate niclosamide activity. Our results encourage further research to understand and optimize niclosamide performance as an anticancer drug substance aiming at its repositioning.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":653,"journal":{"name":"Journal of Nanoparticle Research","volume":"26 9","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nanoparticle Research","FirstCategoryId":"88","ListUrlMain":"https://link.springer.com/article/10.1007/s11051-024-06126-9","RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
The BCS class II (Biopharmaceutical Classification System) niclosamide has shown promising anticancer activity for colorectal cancer. However, its low water solubility compromises its oral absorption and systemic action. Incorporating niclosamide in nanoemulsion allows to optimize its cell uptake and tumor penetration. This study aimed at the development, physicochemical characterization, and in vitro anticancer activity of a niclosamide nanoemulsion, with HCT-116 as the cell model. Medium- and long-chain lipids were tested to prepare the nanoemulsions, obtained by high-pressure homogenization. Design of experiments was used to optimize the formulations, which were subjected to a stability study at 30 °C/75% relative humidity (RH) and 4 °C. Nanoemulsion efficacy was evaluated in an HCT-116 viability assay and 3D cell culture model. Medium-chain lipids provided better solubility results than long-chain. Miglyol® 812 and poloxamer 188 proved to be suitable components for the system. Niclosamide nanoemulsion (~ 200 nm) was stable for 56 days, presenting monomodal particle size distribution. The cell viability assay with HCT-116 cell line demonstrated that niclosamide cytoxicity was both time and concentration dependent. In the 3D cell culture model, size and zeta potential may have influenced drug penetration in the spheroid. Incorporating the drug substance in a nanostructured system was pivotal to potentiate niclosamide activity. Our results encourage further research to understand and optimize niclosamide performance as an anticancer drug substance aiming at its repositioning.
期刊介绍：
The objective of the Journal of Nanoparticle Research is to disseminate knowledge of the physical, chemical and biological phenomena and processes in structures that have at least one lengthscale ranging from molecular to approximately 100 nm (or submicron in some situations), and exhibit improved and novel properties that are a direct result of their small size.
Nanoparticle research is a key component of nanoscience, nanoengineering and nanotechnology.
The focus of the Journal is on the specific concepts, properties, phenomena, and processes related to particles, tubes, layers, macromolecules, clusters and other finite structures of the nanoscale size range. Synthesis, assembly, transport, reactivity, and stability of such structures are considered. Development of in-situ and ex-situ instrumentation for characterization of nanoparticles and their interfaces should be based on new principles for probing properties and phenomena not well understood at the nanometer scale. Modeling and simulation may include atom-based quantum mechanics; molecular dynamics; single-particle, multi-body and continuum based models; fractals; other methods suitable for modeling particle synthesis, assembling and interaction processes. Realization and application of systems, structures and devices with novel functions obtained via precursor nanoparticles is emphasized. Approaches may include gas-, liquid-, solid-, and vacuum-based processes, size reduction, chemical- and bio-self assembly. Contributions include utilization of nanoparticle systems for enhancing a phenomenon or process and particle assembling into hierarchical structures, as well as formulation and the administration of drugs. Synergistic approaches originating from different disciplines and technologies, and interaction between the research providers and users in this field, are encouraged.
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