Study of the micellization behavior of different order amino block copolymers with heparin.
OBJECTIVE
The purpose of this study was to prepare and characterize copolymers presenting different pendant amino groups and to study their ability to form polyelectrolyte complexes with heparin. The responsiveness of the complexes to variations in pH and ionic strength was correlated to the nature of the copolymers.


METHODS
Copolymers composed of different aminoethyl methacrylate monomers were synthesized by atom transfer radical polymerization (ATRP) from a poly(ethylene glycol) macroinitiator. Copolymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Micellization properties were assessed by atomic force microscopy, multiangle static light scattering, and dynamic light scattering on complexes formed from the addition of heparin to a solution of polymer.


RESULTS
Primary, tertiary, and quaternary amine-based diblock copolymers with molecular weights ranging from 4900 to 7400 and low polydispersity indexes were prepared. The synthesis of a copolymer bearing primary amines was achieved for the first time by ATRP. Micellization was found to be pH- and polymer-dependent. All polymers interacted with heparin at acidic pH to yield monodisperse assemblies of less than 30 nm. Complexes dissociated in response to increases in ionic strength.


CONCLUSIONS
Electrostatic interactions between the amino copolymers and heparin triggered the formation of small, monodisperse, and stable complexes that present great potential as oral drug delivery systems.
Dufresne
Marie-Hélène
MH
Faculty of Pharmacy, University of Montreal, P.O. Box 6128, Succ. Centre-Ville, Montreal, Quebec, Canada, H3C 3J7.
Leroux
Jean-Christophe
JC
D000588:Amines / Q000737:chemistry; D006493:Heparin / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry
D000588:Amines; D008823:Micelles; D011109:Polymethacrylic Acids; D011092:Polyethylene Glycols; D006493:Heparin