From well-defined diblock copolymers prepared by a versatile atom transferradical polymerization method to supramolecular assemblies

The synthesis of well-defined diblock copolymers by atom transfer radical p olymerization (ATRP) was explored in detail for the development of new coll oidal carriers. The ATRP technique allowed the preparation of diblock copol ymers of poly(ethylene glycol) (PEG) (number-average molecular weight: 2000 ) and ionic or nonionizable hydrophobic segments. Using monofunctionalized PEG macroinitiator, ionizable and hydrophobic monomers were polymerized to obtain the diblock copolymers. This polymerization method provided good con trol over molecular weights and molecular weight distributions, with monome r conversions as high as 98%. Moreover, the copolymerization of hydrophobic and ionizable monomers using the PEG macroinitiator made it possible to mo dulate the physicochemical properties of the resulting polymers in solution . Depending on the length and nature of the hydrophobic segment, the nonion ic copolymers could self-assemble in water into nanoparticles or polymeric micelles. For example, the copolymers having a short hydrophobic block (5 < degree of polymerization < 9) formed polymeric micelles in aqueous solutio n, with an apparent critical association concentration between 2 and 20 mg/ L. The interchain association of PEG-based polymethacrylic acid derivatives was found to be pH-dependent and occurred at low pH. The amphiphilic and n onionic copolymers could be suitable for the solubilization and delivery of water-insoluble drugs, whereas the ionic diblock copolymers offer promisin g characteristics for the delivery of electrostatically charged compounds ( e.g., DNA) through the formation of polyion complex micelles. Thus, ATRP re presents a promising technique for the design of new multiblock copolymers in drug delivery. (C) 2001 John Wiley & Sons, Inc.