Dipyridamole recognition and controlled release by uniformly sized molecularly imprinted nanospheres Mehdi Esfandyari-Manesh a , Mehran Javanbakht a, b, ⁎, Fatemeh Atyabi c , Ali Mohammadi c, d , Somayeh Mohammadi a , Behrouz Akbari-Adergani e , Rassoul Dinarvand c a Department of Chemistry, Amirkabir University of Technology, Tehran, Iran b Nano Science and Technology Research Center, Amirkabir University of Technology, Tehran, Iran c Nanotechnology Research Center, Tehran University of Medical Sciences, Tehran, Iran d Department of Drug and Food Control, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran e Food and Drug Laboratory Research Center, Food and Drug Department, Ministry of Health and Medical Education, Tehran, Iran abstract article info Article history: Received 13 February 2011 Received in revised form 2 June 2011 Accepted 29 July 2011 Available online 16 August 2011 Keywords: Molecular imprinting Dipyridamole Nanosphere Molecular binding Controlled release We used novel synthetic conditions of precipitation polymerization to obtain uniformly sized molecularly imprinted nanospheres of dipyridamole for application in the design of new drug delivery systems. In addition, the morphology, drug release, and binding properties of molecularly imprinted polymers (MIPs) were studied, and the effects of morphology on other properties were investigated. The MIPs prepared by acetonitrile/chloroform (19:1, v/v) were uniformly sized nanospheres with an average mean diameter of approximately 88 nm at a wetted state, 50 nm at a dry state, and a polydispersity index of 0.062. The imprinted nanospheres showed excellent binding properties and had 62.7% of template binding compared with 17.1% of its blank polymer. The imprinted nanospheres with 67.5 (mg template/of polymer) of binding capacity had better imprinting efficiency than the 50.5% of binding capacity shown by irregularly shaped MIP particles that were prepared by chloroform. The molecular binding abilities of imprinted nanospheres in human serum were evaluated by HPLC analysis (binding about 77% of dipyridamole). Results from release experiments of MIPs showed a very slow, controlled, and satisfactory release of dipyridamole. The loaded drug was released up to 99% in 17 days for nanospheres and 22 days for irregularly shaped particles. © 2011 Elsevier B.V. All rights reserved. 1. Introduction Molecular imprinting is a synthetic approach for generation of artificial receptor-like binding sites in polymeric materials [1–3]. Molecularly imprinted polymers (MIPs) are generated by copolymer- ization of functional monomers with a cross-linker agent in the presence of a template molecule. The functional monomers interact with the template and the functional groups on the monomers are then fixed via the cross-linking polymerization of these monomers. After polymeri- zation, the template is removed from the polymer network to afford binding sites complimentary to the template structure, and the MIPs can then rebind the template with high selectivity. Given the advantage of high binding affinity, easy preparation, and chemical stability, MIPs possess a high potential for use in broad applications such as liquid chromatography [4], capillary electrochromatography [5], solid-phase extraction [6], sensors [7], and drug delivery systems [8]. Recently, research on MIPs has focused on techniques of polymer- ization, the improvement and development of new morphologies and their applications in separation, assay technology, sensors, and biomedical fields [9]. Different applications of MIPs demand different properties from the polymers such as morphology, specificity, capacity, binding, and release properties. In response to this demand, different methods of production of MIPs have been developed. So far, MIPs have been prepared by different methods such as bulk polymerization, suspension polymerization [10], multi-step swelling and polymeriza- tion method [11], core–shell emulsion polymerization [12], miniemul- sion polymerization [13], and precipitation polymerization [14]. Usually, MIPs are prepared by bulk polymerization. In this method, MIPs are synthesized in form of porous monolith that is then ground and sieved to appropriate particle sizes [15]. Suspension and emulsion polymerization can provide spherical particles, but these methods are more complicated processes and the use of additives (such as surfactant) is necessary. Among these methods, precipitation polymer- ization is probably the most facile synthetic method that provides MIP microspheres and nanospheres with sufficient control of the desired characteristics, especially morphology [16]. Mosbach et al. presented a new precipitation polymerization method for preparing uniform MIP microspheres quickly, cleanly, and in good yield [17]. As no interfering reagent (such as a surfactant or stabilizer) was used during the polymer synthesis, the method was found to be generally applicable to various Materials Science and Engineering C 31 (2011) 1692–1699 ⁎ Corresponding author at: Department of Chemistry, Amirkabir University of Technology, Tehran, Iran. Tel.: + 98 21 64543295; fax: + 98 21 64543296. E-mail address: mehranjavanbakht@gmail.com (M. Javanbakht). 0928-4931/$ – see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.msec.2011.07.019 Contents lists available at SciVerse ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec