Production of Highly Crosslinked Microspheres by the Precipitation Polymerization of 2-(Diethylamino)ethyl Methacrylate with Two or Three Functional Crosslinkers Yeliz Tunc, Kezban Ulubayram Department of Basic Pharmaceutical Sciences, Hacettepe University, Sihhiye 06100, Ankara, Turkey Received 7 January 2008; accepted 27 September 2008 DOI 10.1002/app.29390 Published online 2 January 2009 in Wiley InterScience (www.interscience.wiley.com). ABSTRACT: Precipitation polymerizations of 2-(diethy- lamino)ethyl methacrylate were carried out with ethylene glycol dimethacrylate and then trimethylolpropane trimethacrylate in acetonitrile to produce monodisperse, highly crosslinked microspheres. Poly(diethylaminoethyl methacrylate-co-trimethylolpropane trimethacrylate) [poly (DEAEMA-co-TRIM)] microspheres, in the range of 1.2–2.7 lm, were obtained with a total monomer concentration of 1 vol % with respect to the solvent, and they kept their identity with several polymerization parameters. When the total monomer concentration was increased further, indi- vidual particles lost their identity and aggregated. Poly (DEAEMA-co-TRIM) particles with a total monomer con- centration of 1 vol % had more discrete spherical forms with smoother surfaces, whereas in the poly(diethylami- noethyl methacrylate-co-ethylene glycol dimethacrylate) system, sticky microspheres were obtained with a total monomer concentration of 2.1 vol %. Moreover, several polymerization parameters were investigated to control the physical properties of microspheres of poly(DEAEMA- co-TRIM) and to understand the nature of the precipitation polymerization. Thus, the average particle size increased from 2.3 to 2.7 lm with an increased azobisisobutyronitrile concentration and then decreased to about 1.2 lm as the polymerization temperature was increased. All the micro- spheres produced under different polymerization condi- tions were found to be monodisperse (polydispersity index <0.1) with a narrow size distribution. V V C 2009 Wiley Periodicals, Inc. J Appl Polym Sci 112: 532–540, 2009 Key words: copolymerization; crosslinking; microgels; radical polymerization INTRODUCTION Among polymeric materials, microspheres are an im- portant group; they are characterized by their small size and volume, large specific surface area, uniform size, chemistry and morphology, and ability to form stable dispersions. 1 These materials are used in a wide range of medical and biochemical applications, including enzyme immobilization, 2 drug delivery systems, 3 chromatographic separation, 4 immunoas- says, and medical diagnostics. 5,6 All these applica- tions depend on the size, monodispersity, morphology, and surface characteristics of the micro- spheres. Although large microspheres are used as cell culture carriers, smaller ones are used as drug carriers. 1 In addition to the other properties, the monodispersity of the microspheres is crucial in all applications to obtain reproducible results. Therefore, it is important to control their size and uniformity. Polymeric microspheres can be prepared by differ- ent well-known heterogeneous polymerization meth- ods such as emulsion polymerization, suspension polymerization, and dispersion polymerization. Emulsion polymerization produces particles that are 0.01–1 lm in diameter. This heterogeneous polymer- ization involves emulsification of a monomer in water by an emulsifier and initiation by a water or oil-soluble initiator. Because a large oil–water interfa- cial area is formed, a stabilizer (an ionic or nonionic surfactant or protective colloid) is required to prevent coagulation of the particles. 7 Suspension polymeriza- tion is used to prepare large polymer beads with a wide range of diameters (5–1000 lm). In this method, water-soluble monomers may be polymerized with water in oil or the reverse, in which a concentrated aqueous monomer solution is polymerized in a non- polar medium. 8 Surfactants are used to prevent coag- ulation as in emulsion polymerization. If the initial emulsion in the polymerization is polydisperse, then it will produce a broad particle size distribution and thus require a size classification step, which makes the method expensive and causes low reaction yields. 9 Dispersion polymerization, used to prepare polymer microspheres in the range of 1–15 lm, is characterized by its initially homogeneous polymer- ization medium, in which the insoluble polymer is Journal of Applied Polymer Science, Vol. 112, 532–540 (2009) V V C 2009 Wiley Periodicals, Inc. Correspondence to: K. Ulubayram (ukezban@hacettepe. edu.tr). Contract grant sponsor: Scientific Research Unit of Hacettepe University; contract grant number: BAB 06D07301001.