Drug induced micellization into ultra-high capacity and stable curcumin nanoformulations: Physico-chemical characterization and evaluation in 2D and 3D in vitro models.

Autor: Lübtow MM; Functional Polymer Materials, Department of Chemistry and Pharmacy and Bavarian Polymer Institute, Würzburg University, Röntgenring 11, 97070 Würzburg, Germany., Nelke LC; University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany., Seifert J; University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany., Kühnemundt J; University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany., Sahay G; Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, OR 97201, United States; Department of Biomedical Engineering, Oregon Health and Science University, Collaborative Life Science Building, 2730 SW Moody Avenue, Portland, OR 97201, United States., Dandekar G; University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany; Translational Center 'Regenerative Therapies' (TLC-RT), Fraunhofer Institute for Silicate Research (ISC), Neunerplatz 2, 97082 Würzburg, Germany., Nietzer SL; University Hospital Würzburg, Röntgenring 11, 97070 Würzburg, Germany. Electronic address: sarah.nietzer@uni-wuerzburg.de., Luxenhofer R; Functional Polymer Materials, Department of Chemistry and Pharmacy and Bavarian Polymer Institute, Würzburg University, Röntgenring 11, 97070 Würzburg, Germany. Electronic address: robert.luxenhofer@uni-wuerzburg.de.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2019 Jun 10; Vol. 303, pp. 162-180. Date of Electronic Publication: 2019 Apr 11.
DOI: 10.1016/j.jconrel.2019.04.014
Abstrakt: Curcumin (CUR) is a natural extract from the plant Curcuma longa and part of turmeric, a spice and herbal remedy in traditional medicine. Thousands of papers claim a plethora of health benefits by CUR, but a growing number of reports and contributions caution that many experimental data may be artifacts or outright deny any suitability of CUR due to its problematic physicochemical properties. Two major issues often encountered with CUR are its extraordinarily low solubility in water and its limited chemical stability. Here, we report on a novel nanoformulation of CUR that enables CUR concentrations in water of at least 50 g/L with relative drug loadings of >50 wt% and high dose efficacy testing in 3D tumor models. Despite this high loading and concentration, the CUR nanoformulation comprises polymer-drug aggregates with a size <50 nm. Most interestingly, this is achieved using an amphiphilic block copolymer, that by itself does not form micelles due to its limited hydrophilic/lipophilic contrast. The ultra-high loaded nanoformulations exhibit a very good stability, reproducibility and redispersibility. In order to test effects of CUR in conditions closer to an in vivo situation, we utilized a 3D tumor test system based on a biological decellularized tissue matrix that better correlates to clinical results concerning drug testing. We found that in comparison to 2D culture, the invasively growing breast cancer cell line MDA-MB-231 requires high concentrations of CUR for tumor cell eradication in 3D. In addition, we supplemented a 3D colorectal cancer model of the malignant cell line SW480 with fibroblasts and observed also in this invasive tumor model with stroma components a decreased tumor cell growth after CUR application accompanied by a loss of cell-cell contacts within tumor cell clusters. In a flow bioreactor simulating cancer cell dissemination, nanoformulated CUR prevented SW480 cells from adhering to a collagen scaffold, suggesting an anti-metastatic potential of CUR. This offers a rationale that the presented ultra-high CUR-loaded nanoformulation may be considered a tool to harness the full therapeutic potential of CUR.
(Copyright © 2019. Published by Elsevier B.V.)
Databáze: MEDLINE
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