Toxicity Evaluation and Controlled-Release of Curcumin-Loaded Amphiphilic Poly-N-vinylpyrrolidone Nanoparticles: In Vitro and In Vivo Models
Anna L. Luss,
Dmitry V. Bagrov,
Anne V. Yagolovich,
Ekaterina V. Kukovyakina,
Irina I. Khan,
Vadim S. Pokrovsky,
Maria V. Shestovskaya,
Marine E. Gasparian,
Dmitry A. Dolgikh,
Andrey N. Kuskov
Affiliations
Anna L. Luss
Department of Technology of Chemical, Pharmaceutical and Cosmetic Substances, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
Dmitry V. Bagrov
Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
Anne V. Yagolovich
Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
Ekaterina V. Kukovyakina
Department of Technology of Chemical, Pharmaceutical and Cosmetic Substances, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
Irina I. Khan
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 115478 Moscow, Russia
Vadim S. Pokrovsky
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia, 115478 Moscow, Russia
Maria V. Shestovskaya
Department of Technology of Chemical, Pharmaceutical and Cosmetic Substances, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
Marine E. Gasparian
Department of Technology of Chemical, Pharmaceutical and Cosmetic Substances, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
Dmitry A. Dolgikh
Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
Andrey N. Kuskov
Department of Technology of Chemical, Pharmaceutical and Cosmetic Substances, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia
Curcumin attracts huge attention because of its biological properties: it is antiproliferative, antioxidant, anti-inflammatory, immunomodulatory and so on. However, its usage has been limited by poor water solubility and low bioavailability. Herein, to solve these problems, we developed curcumin-loaded nanoparticles based on end-capped amphiphilic poly(N-vinylpyrrolidone). Nanoparticles were obtained using the solvent evaporation method and were characterized by dynamic and electrophoretic light scattering, transmission electron (TEM) and atomic force (AFM) microscopy. The average particle size was 200 nm, and the ζ-potential was −4 mV. Curcumin-release studies showed that nanoparticles are stable in aqueous solutions. An in vitro release study showed prolonged action in gastric, intestinal and colonic fluids, consistently, and in PBS. In vitro studies on epidermoid carcinoma and human embryonic kidney cells showed that the cells absorbed more curcumin in nanoparticles compared to free curcumin. Nanoparticles are safe for healthy cells and show high cytotoxicity for glioblastoma cells in cytotoxicity studies in vitro. The median lethal dose was determined in an acute toxicity assay on zebrafish and was 23 μM. Overall, the curcumin-loaded nanoparticles seem promising for cancer treatment.
