Micellar nanocarriers assembled from doxorubicin-conjugated amphiphilic macromolecules (DOX-AM).
Amphiphilic macromolecules (AMs) have unique branched hydrophobic domains attached to linear PEG chains. AMs self-assemble in aqueous solution to form micelles that are hydrolytically stable in physiological conditions (37 degrees C, pH 7.4) over 4 weeks. Evidence of AM biodegradability was demonstrated by complete AM degradation after 6 d in the presence of lipase. Doxorubicin (DOX) was chemically conjugated to AMs via a hydrazone linker to form DOX-AM conjugates that self-assembled into micelles in aqueous solution. The conjugates were compared with DOX-loaded AM micelles (i.e., physically loaded DOX) on DOX content, micellar sizes and in vitro cytotoxicity. Physically encapsulated DOX loading was higher (12 wt.-%) than chemically bound DOX (6 wt.-%), and micellar sizes of DOX-loaded AMs (approximately 16 nm) were smaller than DOX-AMs (approximately 30 nm). In vitro DOX release from DOX-AM conjugates was faster at pH 5.0 (100%) compared to pH 7.4 (78%) after 48 h, 37 degrees C. Compared to free DOX and physically encapsulated DOX, chemically bound DOX had significantly higher cytotoxicity at 10(-7) M DOX dose against human hepatocellular carcinoma cells after 72 h. Overall, DOX-AM micelles showed promising characteristics as stable, biodegradable DOX nanocarriers.
del Rosario
Leilani S
LS
Department of Chemistry and Chemical Biology, Rutgers University, 610 Taylor Road, Piscataway, New Jersey 08854, USA.
Demirdirek
Bahar
B
Harmon
Alexander
A
Orban
David
D
Uhrich
Kathryn E
KE
D001682:Biological Availability; D002470:Cell Survival / Q000187:drug effects; D003956:Dialysis; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007850:Lauric Acids / Q000737:chemistry; D008027:Light; D008049:Lipase / Q000378:metabolism; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D012542:Scattering, Radiation; D013053:Spectrophotometry; D013400:Sugar Acids / Q000737:chemistry; D013501:Surface-Active Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
D004337:Drug Carriers; D006834:Hydrazines; D007850:Lauric Acids; D008823:Micelles; D013400:Sugar Acids; D013501:Surface-Active Agents; C029424:hydrazine; D011092:Polyethylene Glycols; D004317:Doxorubicin; C000090:galactaric acid; D008049:Lipase