Hydrogen bonding-enhanced micelle assemblies for drug delivery.
Ring-opening polymerization (ROP) of functionalized cyclic carbonates derived from 2,2-bis(methylol)propionic acid (bis-MPA) allows for incorporation of H-bonding urea-functional groups into block copolymers with a potential application of supramolecular drug-delivery systems. The strong H-bonding functionalities of poly(ethylene glycol)-block-poly(ethyl-random-urea carbonate) (PEG-P(E(1-x)-U(x))C) block copolymers not only lowered critical micelles concentration (cmc) of the block copolymer (to 1/4x) in aqueous environment compared to conventional PEG-poly(trimethylene carbonate) (PEG-PTMC) block copolymer without the non-covalent stabilization, but also improved kinetic stability of micelles and Dox-loaded micelles in the presence of a destabilizing agent. It was observed that the incorporation of anticancer drug doxorubicin affected the micellization process of block copolymers in water and caused a sudden increase in sizes of drug-loaded micelles above 200 nm. This phenomenon that can be a significant drawback in drug delivery applications was considerably mitigated in urea-bearing block copolymer/Dox micelles with simultaneously accompanying a significant improvement in drug loading. In vitro drug release profile showed that the increase in urea content led to a slight decrease in Dox release rate. Block copolymer did not have any significant cytotoxicity against HEK293 and HepG2 cells up to 400 mg/L. Importantly, Dox-loaded micelles exerted cytotoxic effect against HepG2 cells.
Kim
Sung Ho
SH
IBM Almaden Research Center, 650 Harry Road, San Jose, CA 95120, USA.
Tan
Jeremy P K
JP
Nederberg
Fredrik
F
Fukushima
Kazuki
K
Colson
John
J
Yang
Chuan
C
Nelson
Alshakim
A
Yang
Yi-Yan
YY
Hedrick
James L
JL
D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002850:Chromatography, Gel; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D008027:Light; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008970:Molecular Weight; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012542:Scattering, Radiation; D014508:Urea / Q000494:pharmacology
D008823:Micelles; D011108:Polymers; D004317:Doxorubicin; D014508:Urea