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Biomacromolecules 2010, 11, 430–438
Poly(DL-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate): Synthesis, Characterization, Micellization Behavior in Aqueous Solutions, and Encapsulation of the Hydrophobic Drug Dipyridamole Nikos Karanikolopoulos, Miljana Zamurovic, Marinos Pitsikalis,* and Nikos Hadjichristidis* Industrial Chemistry Laboratory, Department of Chemistry, University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece Received October 9, 2009; Revised Manuscript Received December 8, 2009
We synthesized a series of well-defined poly(DL-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PDLLAb-PDMAEMA) amphiphilic diblock copolymers by employing a three-step procedure: (a) ring-opening polymerization (ROP) of DL-lactide using n-decanol and stannous octoate, Sn(Oct)2, as the initiating system, (b) reaction of the PDLLA hydroxyl end groups with bromoisobutyryl bromide, and (c) atom transfer radical polymerization, ATRP, of DMAEMA with the newly created bromoisobutyryl initiating site. The aggregation behavior of the prepared block copolymers was investigated by dynamic light scattering and ζ potential measurements at 25 °C in aqueous solutions of different pH values. The hydrophobic drug dipyridamole was efficiently incorporated into the copolymer aggregates in aqueous solutions of pH 7.40. High partition coefficient values were determined by fluorescence spectroscopy.
Introduction Block copolymers have attracted significant scientific and economic interest over the last few decades because of their ability to self-assemble into ordered structures.1 In bulk, selfassembly leads to characteristic morphological patterns (cylinders, spheres, lamellae, gyroid, etc.).1,2 In a selective solvent, that is, a thermodynamically good solvent for the one block and precipitant for the other, block copolymers associate and form micellar aggregates.3 The micelles consist of a more-orless swollen core of the insoluble blocks surrounded by a protective corona of the soluble blocks. A large number of parameters such as temperature, solvent quality, concentration, pH, copolymer structure, molecular weight and composition may affect the aggregation behavior, leading to a wide variety of micellar morphologies (spheres, cylinders, vesicles, lamellae, etc.).3,4 Because of their stability, variety of size, and core-shell structure, micelles can be used in a diverse range of practical applications, such as colloidal stabilization,5 latex technology,6 compatibilization in polymer blends,7 viscosity, and surface modification,8 in environmental science enhancing the solubility of water-insoluble compounds (water purification),9 and so on. However, polymeric micelles have been valuable and studied extensively because of their applications in medicine, mainly as drug delivery vehicles.10 This is attributed to: (a) the high stability of the micelles in aqueous solutions because their low critical micelle concentration (cmc) prevents micelle dissociation upon dilution in the bloodstream, (b) their small size (
