Synthesis and physical gels of pH- and thermo-responsive tertiary amine methacrylate based ABA triblock copolymers and drug release studies Fadime Fulya Taktak a , Vural Bütün b, * a Department of Chemistry, Faculty of Arts and Science, Afyon Kocatepe University, 03200 Afyonkarahisar, Turkey b Department of Chemistry, Faculty of Arts and Science, Eskis ¸ ehir Osmangazi University, 26480 Eskis ¸ ehir, Turkey article info Article history: Received 8 March 2010 Received in revised form 31 May 2010 Accepted 1 June 2010 Available online 11 June 2010 Keywords: ABA triblock copolymer Hydrogels Drug release abstract A series of novel pH-responsive ABA triblock copolymer gelators have been synthesized by using poly[2- (diisopropylamino)ethyl methacrylate] (PDPA) as the A block and poly[2-(dimethylamino)ethyl meth- acrylate] (PDMA) as the B block via group transfer polymerization. While the PDPA-b-PDMA-b-PDPA triblock copolymers are molecularly soluble in acidic aqueous media due to protonation of all tertiary amine groups, they formed either gels by the chain-end hydrophobic interactions with relatively high polymer concentration (10 wt%) or near monodisperse “flower” micelles with low polymer concentration at neutral and basic aqueous solutions. The hydrophobic model drug release was studied in a sustained manner from the gels at pH 7.4 by varying the polymer concentration, the polymer molecular weight and the temperature of the medium. Preliminary studies indicate that both slow, sustained release and fast, triggered release of a model hydrophobic drug, dipyridamole, can be achieved by tuning the solution pH, polymer concentration, polymer molecular weight and temperature of the gel. Ó 2010 Elsevier Ltd. All rights reserved. 1. Introduction In recent years, hydrogels have been intensively studied as controlled drug-delivery systems to deliver the drugs at desirable times and/or specific sites to achieve the therapeutic objective [1e3]. Hydrogels are three-dimensional polymeric networks, made by chemical or physical cross-linking of hydrophilic polymers [4]. Some hydrogels have great response to the external stimuli such as changes in pH, temperature, ionic strength, solvent type, electric and magnetic fields, light and the presence of chelating species and therefore have received extensive attention in the past several decades [5e9]. Potential applications for hydrogels have been reported in the fields of tissue engineering, synthetic extracellular matrix, implantable devices, biosensors, materials controlling the activity of enzymes, phospholipid bilayer destabilizing agents, materials controlling reversible cell attachment, nanoreactors with precisely placed reactive groups in three-dimensional space, smart microfluidics with responsive hydrogels and energy-conversion systems [10e16]. Stimuli-sensitive block copolymer hydrogels have great potential in biomedical and pharmaceutical applications, especially in drug-delivery systems and tissue engineering [17e20]. Among the stimuli in the biomedical applications, temperature and pH are the most popular physical and chemical stimuli, respec- tively. Thus, thermo- and/or pH-responsive block copolymer hydrogels have been intensively studied for biomedical applica- tions in recent years [19,21,22]. The pH-sensitive polymers, which contain the ionizable groups and are also called weak polyelectrolytes, show dramatic changes in degree of ionization and water-solubility at a specific pH (pK a ) [5,23]. Typical pH-sensitive polymers for drug delivery are based on the polymers, such as poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA) [24e28], poly(imine)s [29,30], poly(L-glutamic acid) (PLG) [31], polymers containing sulfonamide groups [32], poly[2- (dialkylamino)ethyl methacrylate]s [23,33e35], biodegradable poly(b-amino ester) (PAE) [36,37], and poly(2-vinylpyridine) (P2VP) [38]. Armes research group has recently reported novel pH-respon- sive ABA triblock copolymer gelators by using poly[2-(diisopropy- lamino)ethyl methacrylate] (PDPA) or poly[2-(diethylamino)ethyl methacrylate] (PDEA) as the A block and poly(2-methacryloyloxy- ethyl phosphorylcholine) (PMPC) as the B block [33,34]. While both types of ABA triblock copolymers are molecularly soluble in acidic aqueous media, their neutral aqueous solutions with relatively high concentration (10 wt%) form a gel by the chain-end hydrophobic interactions. The hydrophobic model drug release was studied in a sustained manner from the gel at pH 7.4 and 37  C by varying the polymer concentration. As compared with the PDEA-b-PMPC-b- PDEA hydrogels, the PDPA-b-PMPC-b-PDPA hydrogels, which * Corresponding author. Tel.: þ90 222 2393750/2751; fax: þ90 222 239357. E-mail address: vbutun@ogu.edu.tr (V. Bütün). Contents lists available at ScienceDirect Polymer journal homepage: www.elsevier.com/locate/polymer 0032-3861/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.polymer.2010.06.010 Polymer 51 (2010) 3618e3626