pH/Reduction Dual-Responsive Oxidized Alginate-Doxorubicin (mPEG-OAL-DOX/Cys) Prodrug Nanohydrogels : Effect of Complexation with Cyclodextrins
Novel biocompatible and biodegradable pH/reduction dual-responsive oxidized alginate-doxorubicin (mPEG-OAL-DOX/Cys) prodrug nanohydrogels were designed for tumor-specific intracellular triggered release of anticancer drug DOX by conjugating DOX via acid-labile Schiff base linkage into the PEGylated...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1992. - 34(2018), 1 vom: 09. Jan., Seite 416-424 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2018
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, Non-U.S. Gov't Alginates Cyclodextrins Disulfides Drug Carriers Hexuronic Acids Hydrogels Prodrugs Doxorubicin mehr... |
| Zusammenfassung: | Novel biocompatible and biodegradable pH/reduction dual-responsive oxidized alginate-doxorubicin (mPEG-OAL-DOX/Cys) prodrug nanohydrogels were designed for tumor-specific intracellular triggered release of anticancer drug DOX by conjugating DOX via acid-labile Schiff base linkage into the PEGylated oxidized alginate (mPEG-OAL) cross-linked with bioreducible disulfide bond. The effect of the complexation with cyclodextrins (α-CD and β-CD) before or after the cross-linking of the mPEG-OAL on the DOX content and controlled release performance was investigated. It was found that the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(CD)-OAL-DOX/Cys, prepared by cross-linking of the mPEG-OAL after complexation with cyclodextrins, exhibited better pH/reduction dual-responsive controlled release performance than the mPEG-OAL-DOX/Cys(CD) ones prepared by cross-linking of the mPEG-OAL before complexation with cyclodextrins, owing to the supramolecular cross-linking of the adjacent pseudopolyrotaxanes. Especially for the cyclodextrin inclusion complex prodrug nanohydrogels mPEG(α-CD)-OAL-DOX/Cys, DOX was released rapidly under lower pH media mimicking the tumor microenvironment and completely released within 48 h, while the premature leakage under the simulated physiological condition was ∼40%, without burst release in both cases. The cellular toxicity and uptake results demonstrated that the mPEG(α-CD)-OAL-DOX/Cys prodrug nanohydrogels possessed similar inhibition against cancer cell growth in comparison with the free DOX and enhanced drug intracellular accumulation |
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| Beschreibung: | Date Completed 11.09.2018 Date Revised 02.12.2018 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/acs.langmuir.7b03990 |