Magnetic Nanoparticles for the Delivery of Dapagliflozin to Hypoxic Tumors: Physicochemical Characterization and Cell Studies
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28924948
DOI
10.1208/s12249-017-0874-2
PII: 10.1208/s12249-017-0874-2
Knihovny.cz E-zdroje
- Klíčová slova
- cytotoxicity, dapagliflozin, drug targeting, hypoxia, magnetic nanoparticles, tumor,
- MeSH
- benzhydrylové sloučeniny aplikace a dávkování chemie MeSH
- buňky A549 MeSH
- glifloziny MeSH
- glukosidy aplikace a dávkování chemie MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- magnetické nanočástice aplikace a dávkování chemie MeSH
- nádorová hypoxie účinky léků fyziologie MeSH
- nádorové buněčné linie MeSH
- nanomedicína metody MeSH
- nosiče léků aplikace a dávkování chemie MeSH
- transportér 2 pro sodík a glukózu MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- benzhydrylové sloučeniny MeSH
- dapagliflozin MeSH Prohlížeč
- glifloziny MeSH
- glukosidy MeSH
- magnetické nanočástice MeSH
- nosiče léků MeSH
- SLC5A2 protein, human MeSH Prohlížeč
- transportér 2 pro sodík a glukózu MeSH
In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors. The magnetic nanoparticles consisted of a magnetic iron oxide core and a poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (PMAA-g-PEGMA) polymeric shell. The drug (dapagliflozin) molecules were conjugated on the surface of these nanoparticles via in vivo hydrolysable ester bonds. The nanoparticles had an average size of ~ 70 nm and exhibited a DAPA loading capacity 10.75% (w/w) for a theoretical loading 21.68% (w/w). The magnetic responsiveness of the nanoparticles was confirmed with magnetophoresis experiments. The dapagliflozin-loaded magnetic nanoparticles exhibited excellent colloidal stability in aqueous and biological media. Minimal (less than 15% in 24 h) drug release from the nanoparticles occurred in physiological pH 7.4; however, drug release was significantly accelerated in pH 5.5. Drug release was also accelerated (triggered) under the influence of an alternating magnetic field. The DAPA-loaded nanoparticles exhibited higher in vitro anticancer activity (cytotoxicity) against A549 human lung cancer cells than free DAPA. The application of an external magnetic field gradient increased the uptake of nanoparticles by cells, leading to increased cytotoxicity. The results justify further in vivo studies of the suitability of DAPA-loaded magnetic nanoparticles for the treatment of hypoxic tumors.
Department of Materials Science University of Patras 26504 Patras Greece
Department of Pharmacy Medical School University of Patras 26504 Patras Greece
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