Carbohydrate Polymers 81 (2010) 799–804 Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol The effects of reaction conditions on block copolymerization of chitosan and poly(ethylene glycol) F. Ganji a,b,∗ , M.J. Abdekhodaie a a Department of Chemical Engineering, Sharif University of Technology, Tehran, Iran b Chemical Engineering Department, Faculty of Engineering, Tarbiat Modares University, Tehran, Iran article info Article history: Received 4 October 2009 Received in revised form 24 February 2010 Accepted 25 March 2010 Available online 2 April 2010 Keywords: Chitosan PEG Block copolymer Reaction parameters abstract A novel injectable in situ gelling thermosensitive chitosan-block-poly(ethylene glycol) formulation was synthesized for drug delivery applications. Block copolymerization of monomethoxy–poly(ethylene gly- col) onto chitosan using potassium persulfate as an initiator was carried under a nitrogen atmosphere in aqueous solution. The effects of potassium persulfate and poly(ethylene glycol) concentrations, reaction time and reaction temperature on block polymerization were studied by determining the yield of reaction (%Y), polymerization efficiency (%E) and add-on percentage (%Add-on). Keeping the other conditions con- stant, the optimum reaction conditions were found to be initiator = 0.01 M, reaction temperature = 60 ◦ C and reaction time = 6 h. © 2010 Elsevier Ltd. All rights reserved. 1. Introduction Hydrogels are a unique class of macromolecular networks that can contain a large fraction of aqueous solvent within their structure. The ability of hydrogels to simulate biological tissues makes them suitable for biomedical and pharmaceutical appli- cations (Hoare & Kohane, 2008; Peppas, Hilt, Khademhosseini, & Langer, 2006). Interestingly, the aqueous solutions within some hydrogels undergo a sol–gel transition in response to certain stimuli. Therapeutic agents such as drugs, cells or proteins could be mixed into a sol state and injected using a syringe into the subcutaneous layers of a diseased site to form a depot system (Ganji & Vasheghani-Farahani, 2009). These minimally invasive, in situ gelling injection systems are an advantageous alterna- tive to surgical procedures. Therefore, in situ gelling hydrogels have gained considerable interest for pharmaceutical and biomed- ical applications and have been reviewed from different points of view (He, Kim, & Lee, 2008; Jeong & Gutowska, 2002; Ulijn, 2006; Van-Tomme, Storm, & Hennink, 2008). Thermally reversible hydrogels, which make gels in response to finite temperature changes, have gained the most interest (Ruel-Gariépy & Leroux, 2004; Schmaljohann, 2006; Vermonden, Besseling, Steenbergen, & van Hennink, 2006). Tri-block copolymers of poly(ethylene ∗ Corresponding author at: Chemical Engineering Department, Faculty of Engi- neering, Tarbiat Modares University, P.O. Box: 14115-143, Tehran, Iran. Tel.: +98 21 82884383; fax: +98 21 82883381. E-mail address: fganji@modares.ac.ir (F. Ganji). oxide)–poly(propylene oxide)–poly(ethylene oxide), which are available as Poloxamers or Pluronics, are the most widely used ther- mally reversible hydrogels (Jeong, Kim, & Bae, 2002; Xiong, Tam, & Gan, 2006). The aqueous solution within Poloxamers demonstrates a phase transition from sol to gel between 5 and 30 ◦ C and from gel to sol between 35 and 50 ◦ C, with the temperature increasing monotonically over a polymer concentration range of 20–30 wt%. Chitosan is the biopolymer that is most widely used as a ther- mosensitive hydrogel (Muzzarelli et al., 2007). Chitosan is obtained by alkaline deacetylation of chitin, a cellulose-like polysaccharide that is extracted from the shells of crustaceans such as crabs, shrimps and lobsters (Muzzarelli & Muzzarelli, 2009). Although chitin is completely insoluble in aqueous media, chitosan can be dissolved under acidic conditions that provide sufficient proto- nation of its amino groups. The resulting aqueous solutions are usually stable as long as the pH is below 6.2 (Chenite, Gori, Shive, Desrosiers, & Buschmann, 2006). When the pH exceeds 6.2, chi- tosan solutions can be neutralized by glycerol phosphate disodium salt solutions, which leads to the formation of a hydrated gel- like precipitate (Chenite, Buschmann, Wang, Chaput, & Kandani, 2001). Chitosan–glycerophosphate solutions exhibit reverse ther- mogelling properties: they are sols at room temperature and gels at body temperature (Chenite et al., 2000; Ganji, Abdekhodaie, & Ramazany-Sadtabadi, 2007). A thermosensitive sol–gel solution was also obtained by grafting polymerization of N-isopropylacrylamide (NIPAAm) onto chitosan (Lee, Jung, Park, Park, & Ryu, 2004). The maximum grafted chi- tosan copolymer was obtained with 0.4 M NIPAAm and 6 × 10 −3 M cerium ammonium nitrate as an initiator. 0144-8617/$ – see front matter © 2010 Elsevier Ltd. All rights reserved. doi:10.1016/j.carbpol.2010.03.049