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Langmuir 2007, 23, 4214-4224
pH-Responsive Aggregates from Double Hydrophilic Block Copolymers Carrying Zwitterionic Groups. Encapsulation of Antiparasitic Compounds for the Treatment of Leishmaniasis Nikos Karanikolopoulos, Marinos Pitsikalis,* and Nikos Hadjichristidis* Industrial Chemistry Laboratory, Department of Chemistry, UniVersity of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece
Kalliopi Georgikopoulou and Theodora Calogeropoulou Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vassileos Constantinou AVenue, 11635 Athens, Greece
John R. Dunlap UniVersity of Tennessee, Program Microscopy, KnoxVille, Tennessee 37996 ReceiVed October 2, 2006. In Final Form: December 22, 2006 A series of well-defined poly[(ethylene oxide)-b-2-(dimethylamino)ethyl methacrylate] (PEO-b-PDMAEMA) diblock copolymers were synthesized by atom transfer radical polymerization (ATRP) techniques. Post-polymerization reactions were performed to transform a portion of the tertiary amine groups of the PDMAΕMA into phosphorozwitterions. The aggregation behavior of the prepared zwitterionic block copolymers was investigated by static and dynamic light scattering techniques at 25 and 37 °C, in weakly basic and acidic aqueous solutions. Antiparasitic drugs used for the treatment of Leishmania were incorporated into the copolymer aggregates. The effect of the solution pH, the zwitterion content, temperature, and the quantity of the incorporated drug on the aggregation behavior of the copolymers was tested.
Introduction One of the most intriguing features of block copolymers is their ability to self-assemble either in bulk or in selective solvents.1 In bulk, self-assembly leads to characteristic morphological patterns (cylinders, spheres, lamellae, gyroids, etc.),1,2 whereas, in selective solvents, micelle formation has been reported.3 The micelles consist of a more or less 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 molecular weight, and composition may affect the aggregation behavior, leading to a wide variety of micellar morphologies (spheres, cylinders, vesicles, lamellae, etc.).3,4 Special interest has been focused on the area of aqueous micellar systems, due to the wide range of their potential applications, such as detergency, surface coating, wastewater treatment, and oil recovery.5 However, the most valuable application involves the use of aqueous micellar solutions in controlled drug delivery. Amphiphilic block copolymer micelles have emerged as carriers for poorly water soluble drugs through the incorporation * Corresponding author. (1) (a) Hadjichristidis, N.; Pispas, S.; Floudas, G. Block Copolymers; WileyInterscience: New York, 2003. (b) Hamley, I. W. The Physics of Block Copolymers; Oxford University Press: New York, 1998. (2) (a) Abetz, V.; Simon, P. F. W. AdV. Polym. Sci. 2005, 189, 125. (b) Hadjichristidis, N.; Iatrou, H.; Pitsikalis, M.; Pispas, S.; Avgeropoulos, A. Prog. Polym. Sci. 2005, 30, 725. (3) (a) Gohy, J. F. AdV. Polym. Sci. 2005, 190, 65. (b) Riess, G. Prog. Polym. Sci. 2003, 28, 1107. (c) Hamley, I. W. Nanotechnology 2003, 14, R39. (d) Chen, D.; Jiang, M. Acc. Chem. Res. 2005, 38, 494. (e) Dwars, T.; Paetzold, E.; Oehme, G. Angew. Chem. Int. Ed. 2005, 44, 7174.
of these compounds in the inner micellar core.6 These drug vehicles offer several attractive characteristics, such as (a) small size (
