Autor: |
M, Konhäuser, V K, Kannaujiya, E, Steiert, K, Schwickert, T, Schirmeister, P R, Wich |
Rok vydání: |
2022 |
Předmět: |
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Zdroj: |
International Journal of Pharmaceutics. 622:121796 |
ISSN: |
0378-5173 |
DOI: |
10.1016/j.ijpharm.2022.121796 |
Popis: |
Co-encapsulation of multiple therapeutic drugs in a single nanocarrier has the potential to enable synergistic interactions, increase drug efficacy, and reduce side effects. The enzyme l-asparaginase and the small molecule drug etoposide have a known synergistic effect against selected cancer types. However, both drugs differ significantly in size, molecular weight, and solubility, which often results in challenges when a simultaneous delivery is required. In this study, we present the co-encapsulation of a large hydrophilic enzyme l-asparaginase and the small hydrophobic drug etoposide into a biodegradable, biocompatible, and acid-responsive dextran-based nanoparticle system. These dual drug-loaded nanoparticles show an excellent cellular uptake in chronic myeloid leukemia (CML) K562 cells and a stepwise release of the cytotoxic payloads in a pH-dependent manner. In activity tests, the dual drug-loaded formulation has shown a significant effect on cell viability (down to 31%) compared to those incubated only with l-asparaginase (92%) or etoposide (82%) at a particle concentration of 125 μg∙mL |
Databáze: |
OpenAIRE |
Externí odkaz: |
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