A pH and redox dual stimuli-responsive poly(amino acid) derivative for controlled drug release
Drug Carriers
Antibiotics, Antineoplastic
Cell Survival
Polymers
Hydrogen-Ion Concentration
01 natural sciences
0104 chemical sciences
Drug Liberation
Drug Delivery Systems
Doxorubicin
Delayed-Action Preparations
Humans
Amino Acids
Oxidation-Reduction
Micelles
HeLa Cells
DOI:
10.1016/j.colsurfb.2016.06.038
Publication Date:
2016-06-24T02:59:30Z
AUTHORS (4)
ABSTRACT
A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring-opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl)-imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and π-π interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release.
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