Model of drug-loaded fluorocarbon-based micelles studied by electron-spin induced (19)f relaxation NMR and molecular dynamics simulation.
Rf-IPDU-PEGs belong to a class of fluoroalkyl-ended poly(ethylene glycol) polymers (Rf-PEGs), where the IPDU (isophorone diurethane) functions as a linker to connect each end of the PEG chain to a fluoroalkyl group. The Rf-IPDU-PEGs form hydrogels in water with favorable sol-gel coexistence properties. Thus, they are promising for use as drug delivery agents. In this study, we introduce an electron-spin induced 19F relaxation NMR technique to probe the location and drug-loading capacity for an electron-spin labeled hydrophobic drug, CT (chlorambucil-tempol adduct), enclosed in the Rf-IPDU-PEG micelle. With the assistance of molecular dynamics simulations, a clear idea regarding the structures of the Rf-IPDU-PEG micelle and its CT-loaded micelle was revealed. The significance of this research lies in the finding that the hydrophobic drug molecules were loaded within the intermediate IPDU shells of the Rf-IPDU-PEG micelles. The molecular structures of IPDU and that of CT are favorably comparable. Consequently, it appears that this study opens a window to modify the linker between the Rf group and the PEG chain for achieving customized structure-based drug-loading capabilities for these hydrogels, while the advantage of the strong affinity among the Rf groups to hold individual micelles together and to interconnect the micellar network is still retained in hopes of maintaining the sol-gel coexistence of the Rf-PEGs.
Mathias
Errol V
EV
Department of Chemistry and Biochemistry, California State University Los Angeles, Los Angeles, California 90032, USA.
Liu
Xiangli
X
Franco
Osmundo
O
Khan
Imran
I
Ba
Yong
Y
Kornfield
Julia A
JA
D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry*; D002699:Chlorambucil / Q000008:administration & dosage; D003497:Cyclic N-Oxides / Q000008:administration & dosage; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems; D005465:Fluorocarbon Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D008823:Micelles; D008958:Models, Molecular; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry; D013113:Spin Labels; D013816:Thermodynamics
D001672:Biocompatible Materials; D003497:Cyclic N-Oxides; D003512:Cyclohexanones; D004337:Drug Carriers; D005465:Fluorocarbon Polymers; D008823:Micelles; D013113:Spin Labels; D002699:Chlorambucil; C005940:isophorone; D011092:Polyethylene Glycols; C001803:tempol