Redox-sensitive disassembly of amphiphilic copolymer based micelles.
Amphiphilic polymers of different hydrophilic-lipophilic ratios were prepared by free radical polymerization using two monomers consisting of triethylene glycol as the hydrophilic part and an alkyl chain connected by disulfide bond as the hydrophobic part. These polymers form micelle-like nanoassemblies in aqueous media and can encapsulate hydrophobic drug molecules up to 14% of their mass. In a reducing environment, these polymeric micelles disassemble and dissolve in water, since the amphiphilic polymers are converted into hydrophilic polymers upon cleavage of the disulfide bond. This disassembly event results in the release of hydrophobic molecules that had been encapsulated inside the micelle, the rate of which was found to be dependent on the concentration of the reducing agent, glutathione (GSH). In vitro experiments also show that the GSH-dependent release of the doxorubicin can be used to effect cytotoxicity in MCF-7 cells.
Ryu
Ja-Hyoung
JH
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Roy
Raghunath
R
Ventura
Judy
J
Thayumanavan
S
S
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D008823:Micelles; D010084:Oxidation-Reduction; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D008823:Micelles; D011108:Polymers; D013501:Surface-Active Agents; D004317:Doxorubicin; D005978:Glutathione