Curcumin nanonization using an alternative small-scale production unit: selection of proper stabilizer applying basic physicochemical consideration and biological activity assessment of nanocrystals

Author:

Nikolić Ines1,Antić-Stanković Jelena2,Božić Dragana2,Randjelovic Danijela3,Marković Bojan4,Lunter Dominique Jasmin5,Kremenović Aleksandar6,Savić Miroslav7,Savić Snežena8

Affiliation:

1. Department of Pharmaceutical Technology and Cosmetology , University of Belgrade – Faculty of Pharmacy , 11000 Belgrade , Serbia

2. Department of Microbiology and Immunology , University of Belgrade – Faculty of Pharmacy , 11000 Belgrade , Serbia

3. Institute of Chemistry, Technology and Metallurgy, Department of Microelectronic Technologies , University of Belgrade , 11000 Belgrade , Serbia

4. Department of Pharmaceutical Chemistry , University of Belgrade – Faculty of Pharmacy , 11000 Belgrade , Serbia

5. Institute of Pharmaceutical Technology , Eberhard-Karls University , D-72076 Tübingen , Germany

6. Laboratory of Crystallography , Faculty of Mining and Geology , University of Belgrade , 11000 Belgrade , Serbia

7. Department of Pharmacology , University of Belgrade – Faculty of Pharmacy , 11000 Belgrade , Serbia

8. Department of Pharmaceutical Technology and Cosmetology , University of Belgrade – Faculty of Pharmacy , 11000 Belgrade , Serbia ; Tel.: +381-11-3951288; Fax: +381-11-3972840

Abstract

Abstract As the number of poorly soluble drugs is increasing, nanocrystals have become very interesting due to wide range of application possibilities. Curcuminwas used as a model active ingredient in this work. Even though it has many proven positive effects, due to its physicochemical issues, its possibilities have not been fully exploited. The goal of this work was to select optimal conditions for a top-down method for curcumin nanosuspension production, and to perform their comprehensive characterization applying complementary methodologies: dynamic light scattering, polarization and atomic force microscopy, thermal analysis, X-ray powder diffraction, antioxidant activity evaluation, release kinetics assessment, and screening of potential biological effects applying cell viability assays on normal human lung fibroblasts, human melanoma and human adenomacarcinoma cells. After 30 min of milling, nanosuspensions stabilized by polysorbate 80 and by its combinations with sucrose palmitate showed good stability, while curcumin crystal structure was unaltered. Obtained nanocrystals were well defined, with average diameter 120–170 nm and PDI of about 0.25, zeta potential was below −30 mV and pH~5 for all formulations. Nanodispersions exhibited high antioxidant potential and improved dissolution rate compared to the corresponding coarse dispersions. Although curcumin nanodispersions exhibited significant antiproliferative effect to each cancer cell line, the highest effect was towards adenocarcinoma cells.

Publisher

Walter de Gruyter GmbH

Subject

Condensed Matter Physics,General Materials Science

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