Communication Macromolecular Rapid Communications wileyonlinelibrary.com 1 DOI: 10.1002/marc.201300585 1. Introduction Drug vehicles [1–4] have a significant impact on the treat- ment and potential cure of many chronic diseases, including cancer, [5] diabetes, [6] and drug addiction. [7,8] However, the poor controllability and fast release of drugs make it difficult to achieve the essential requirements and can damage the therapeutic expression of drugs. [9] Nor- mally, drugs are managed at a high dose at a given time. This is not economical and results in side effects. Sustained release technology allows patients to take certain types of medication less frequently. Increasing attention has been focused on methods to render drug release for a prolonged period of time in a controlled fashion. There are different types of polymeric drug delivery vehicles, including hydrogels, [10–13] homopolymers, [14,15] copolymers, [16,17] polymeric micelles, [18–21] liposomes, [22] nanoparticles, [23] and dendrimers. [24] During the last few decades, much effort has been focused on designing hydrogels for controlled drug release. [25] Hydrogels are a topic of interest for biomaterial researchers due to their biocompatibility, biodegradability, and hydrophi- licity. [26–29] Hydrogels can swell up to many times their dry weight depending on the nature of their functional moieties, cross-linking density, and pH environment. To achieve better chemotherapeutic outcomes, hydrogels should be able to release drugs to a specific site while maintaining concentration at the optimal level required for effectiveness over a specific period of time. [30] In this study, we report the preparation of triazole- containing hydrogels (TGs) that swell gradually in water. The time-dependent increase in swelling was attrib- uted to hydrophobic aggregations caused mainly by π– π stacking [12,31] between triazole rings. This structure was gradually disrupted by water molecules penetrating into the hydrophobic domain, which allowed hydrogen bond formation between one of the nitrogen atoms on the triazole ring and the surrounding water molecules. [12] To the best of our knowledge, this is the first observation of gradual hydrogel swelling in water due to time elapsing and without chemical modifications such as hydrolysis. One of our ultimate goals is to develop a universal drug carrier with time-dependent drug release properties. This triazole-ring-containing hydrogel and its environ- mental responsive behavior can provide a route for time- dependent sustained drug release. The purpose of this study is to develop novel triazole-containing hydrogels (TGs) as drug car- rier and to investigate the sustained drug release accomplished by their time-dependent swelling behavior. The synthetic pathway of TGs includes: (1) DCC-coupling on hydroxyethyl methacrylate (HEMA) to prepare HEMA-alkyne (HA), (2) click- coupling to prepare a triazole-ring-containing monomer (TM), and (3) the synthesis of a series of TGs. The aggrega- tion between triazole rings is found to be responsible for drug release controllability. Rhodamine 6G is studied as a model anticancer drug for release experiments. The effects of pH and temperature on the properties of sustained drug release are also studied. Triazole-Containing Hydrogels for Time- Dependent Sustained Drug Release Vivek Mishra, Seo-Hyun Jung, Jong Mok Park, Han Mo Jeong, Hyung-il Lee* Dr. V. Mishra, Prof. H. M. Jeong, Dr. H.-I. Lee Department of Chemistry, University of Ulsan, Ulsan 680-749, Republic of Korea E-mail: sims0904@ulsan.ac.kr S.-H. Jung, Dr. J. M. Park Research Center for Green Fine Chemicals, Korea Research Institute of Chemical Technology , Ulsan 681-802, Republic of Korea TGs showing - stacking Dye-loaded TGs with - stacking Sustained dye release after relaxing of - stacking (36-48%) 5 days O O O O N N N N Triazole-containing Monomer (TM) Crosslinker O O O O AIBN, 60°C, Toluene Triazole-containing hydrogel (TG) Early View Publication; these are NOT the final page numbers, use DOI for citation !! Macromol. Rapid Commun. 2013, DOI: 10.1002/marc.201300585 © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim