{"title":"Colloidal formulations of etoposide based on self-assembling oleyl-hyaluronan-based structures: Optimization of technology and in vitro analysis","authors":"M.M. Antonova , S.Sh. Karshieva , A.A. Nikitin , Yu.A. Malinovskaya , D.V. Ermolin , A.S. Novikov , E.V. Skorb , D.V. Beigulenko , T.S. Kovshova , E.A. Kalacheva , A.A. Filin , S.E. Gelperina , Yu.V. Ermolenko","doi":"10.1016/j.nanoso.2025.101443","DOIUrl":null,"url":null,"abstract":"<div><div>The ability of the conjugate of hyaluronic acid and oleic acid (oleyl hyaluronan — HA-C18:1) to form self-assembling micellar structures was utilized to enhance the water solubility of the anticancer drug etoposide (ETP) and its prodrug, 4-O′-benzyloxycarbonyl derivative (ETP-Cbz). Using density functional theory (DFT), it was established that the ETP-Cbz associate with HA-C18:1 had greater thermodynamic stability compared to the ETP associate, which was confirmed experimentally. The micelles loaded with ETP-Cbz were smaller (268 nm compared to 407 nm), more stable (with the critical micelle concentration (CMC) decreasing from 0.07 to 0.025 mg/mL), and had the higher drug loading efficiency (82 %) as compared to HA-C18:1/ETP micelles. In vitro experiments showed that both micellar formulations exhibited low hemolytic activity and delayed drug release profiles during the first hours. In vitro cytotoxicity against MCF-7 and MDA-MB-231 cell lines showed the dose-dependent decrease in cell viability whereas the toxic effect against normal human dermal fibroblasts (NHDF) was significantly lower and exceeded the concentration of HA-C18:1 in the micellar formulations. Confocal microscopy was used to confirm the active uptake of micellar formulations by MDA-MB-231 cells. These findings, therefore, suggest that HA-C18:1 may be a promising solubilizing agent for etoposide and its prodrug.</div></div>","PeriodicalId":397,"journal":{"name":"Nano-Structures & Nano-Objects","volume":"41 ","pages":"Article 101443"},"PeriodicalIF":5.4500,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nano-Structures & Nano-Objects","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352507X25000137","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Physics and Astronomy","Score":null,"Total":0}
引用次数: 0
Abstract
The ability of the conjugate of hyaluronic acid and oleic acid (oleyl hyaluronan — HA-C18:1) to form self-assembling micellar structures was utilized to enhance the water solubility of the anticancer drug etoposide (ETP) and its prodrug, 4-O′-benzyloxycarbonyl derivative (ETP-Cbz). Using density functional theory (DFT), it was established that the ETP-Cbz associate with HA-C18:1 had greater thermodynamic stability compared to the ETP associate, which was confirmed experimentally. The micelles loaded with ETP-Cbz were smaller (268 nm compared to 407 nm), more stable (with the critical micelle concentration (CMC) decreasing from 0.07 to 0.025 mg/mL), and had the higher drug loading efficiency (82 %) as compared to HA-C18:1/ETP micelles. In vitro experiments showed that both micellar formulations exhibited low hemolytic activity and delayed drug release profiles during the first hours. In vitro cytotoxicity against MCF-7 and MDA-MB-231 cell lines showed the dose-dependent decrease in cell viability whereas the toxic effect against normal human dermal fibroblasts (NHDF) was significantly lower and exceeded the concentration of HA-C18:1 in the micellar formulations. Confocal microscopy was used to confirm the active uptake of micellar formulations by MDA-MB-231 cells. These findings, therefore, suggest that HA-C18:1 may be a promising solubilizing agent for etoposide and its prodrug.
期刊介绍:
Nano-Structures & Nano-Objects is a new journal devoted to all aspects of the synthesis and the properties of this new flourishing domain. The journal is devoted to novel architectures at the nano-level with an emphasis on new synthesis and characterization methods. The journal is focused on the objects rather than on their applications. However, the research for new applications of original nano-structures & nano-objects in various fields such as nano-electronics, energy conversion, catalysis, drug delivery and nano-medicine is also welcome. The scope of Nano-Structures & Nano-Objects involves: -Metal and alloy nanoparticles with complex nanostructures such as shape control, core-shell and dumbells -Oxide nanoparticles and nanostructures, with complex oxide/metal, oxide/surface and oxide /organic interfaces -Inorganic semi-conducting nanoparticles (quantum dots) with an emphasis on new phases, structures, shapes and complexity -Nanostructures involving molecular inorganic species such as nanoparticles of coordination compounds, molecular magnets, spin transition nanoparticles etc. or organic nano-objects, in particular for molecular electronics -Nanostructured materials such as nano-MOFs and nano-zeolites -Hetero-junctions between molecules and nano-objects, between different nano-objects & nanostructures or between nano-objects & nanostructures and surfaces -Methods of characterization specific of the nano size or adapted for the nano size such as X-ray and neutron scattering, light scattering, NMR, Raman, Plasmonics, near field microscopies, various TEM and SEM techniques, magnetic studies, etc .