Magnetic Nanoparticles for the Delivery of Dapagliflozin to Hypoxic Tumors: Physicochemical Characterization and Cell Studies

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F18%3A73588032" target="_blank" >RIV/61989592:15310/18:73588032 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1208/s12249-017-0874-2" target="_blank" >https://link.springer.com/article/10.1208/s12249-017-0874-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1208/s12249-017-0874-2" target="_blank" >10.1208/s12249-017-0874-2</a>

Result language

angličtina

Original language name

Magnetic Nanoparticles for the Delivery of Dapagliflozin to Hypoxic Tumors: Physicochemical Characterization and Cell Studies

Original language description

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 similar to 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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

—

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

AAPS PHARMSCITECH

ISSN

1530-9932

e-ISSN

—

Volume of the periodical

19

Issue of the periodical within the volume

2

Country of publishing house

US - UNITED STATES

Number of pages

13

Pages from-to

621-633

UT code for WoS article

000423720400012

EID of the result in the Scopus database

2-s2.0-85029573242