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Home > Past Issue

Journal of Applied Pharmaceutical Science Volume: 3, Issue: 6, June, 2013
DOI: 10.7324/JAPS.2013.3601
ISSN 2231-3354

Research Article

Reductant-dependent None-Partial-Complete Degradation of Block Copolymer Disulfide Crosslinked Nanoassemblies

Geun-woo Jin and Younsoo Bae

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Disulfide crosslinked nanoassemblies (ssCNAs) were characterized in this study to assess their reductant-dependent degradation patterns for future development of redox-responsive smart nanomaterials in biomedical applications. The nanoassemblies were prepared from poly(ethylene glycol)-poly(aspartate) block copolymers, crosslinked with cystamine through an amidation reaction, generating 25 nm particles that have a disulfide crosslinked core enveloped with a poly(ethylene glycol) shell. ssCNAs remained unexpectedly stable in the presence of glutathione, a natural reductant overexpressing inside cells to cleave disulfide compounds. Further investigation revealed that ssCNAs underwent none, partial, and complete degradation in aqueous solutions at 37 °C for 48 h, depending on the molecular weight (MW), Connolly surface excluded volume (SEV), and charged state (net negative, neutral, and positive) of a reductant. Among six reductants tested, 2-aminoethanethiol (MW = 77.2, SEV = 52.2 Å3, net positive) was the most efficient for complete degradation of ssCNAs in 1 h, whereas another reductant, similar in structure except the charged state, 2-mercaptoethanol (MW = 78.1, SEV = 50.3 Å3, net neutral), took 4 h for complete nanoassembly degradation. These results indicate that degradation patterns of ssCNAs can be fine-tuned in a reductant-dependent manner, providing a better understanding of chemical stability of disulfide-crosslinked nanoassemblies.

Keywords: Nanoassemblies, disulfide crosslinking, nanoparticles, degradable linkers, drug delivery, gene delivery.