Redox-responsive degradable prodrug nanogels for intracellular drug delivery by crosslinking of amine-functionalized poly(N-vinylpyrrolidone) copolymers.

Facile approaches for the development of new tailored drug carriers are of high importance for the controlled administration of drugs. Herein we report a method for the synthesis of water-soluble reactive copolymers with well-defined architectures for fabrication of redox-sensitive degradable prodrug nanogels for intracellular drug release. Primary amine-functionalized statistical copolymers were obtained by hydrolysis of poly(N-vinylpyrrolidone-co-N-vinylformamide) copolymers which were synthesized via Reversible Addition-Fragmentation chain-Transfer (RAFT) polymerization. Redox-sensitive degradable nanogels with varying crosslinking densities were synthesized with a redox-sensitive cross-linker. Doxorubicin (DOX) was loaded to form prodrug nanogels (DNG) with hydrodynamic radius from 142 nm to 240 nm. The nanogels demonstrated slower degradation and retarded drug release rate with increased crosslinking density in the presence of 10 mM reduced glutathione (GSH) at 37 °C. The in vitro release studies revealed that maximum 85% DOX was released in 24 h under a reductive environment. Intracellular drug release profiles in HeLa cells indicated that the DOX delivery rate was tunable via varying crosslinking density of the nanogels. Cell viability assay demonstrated that the blank nanogels were biocompatible in wide concentrations up to 0.5 mg/mL while the DOX-loaded nanogels displayed medium antitumor activity with IC50 (half-maximal inhibitory concentration) of 1.80 μg/mL, 2.57 μg/mL, 3.01 μg/mL for DNG5, DNG10 and DNG15 respectively.

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.