Synthesis and characterization of thiolated carboxymethyl chitosan-graft-cyclodextrin nanoparticles as a drug delivery vehicle for albendazole Ghazaleh Alamdarnejad • Alireza Sharif • Shahrouz Taranejoo • Mohsen Janmaleki • Mohammad Reza Kalaee • Mohsen Dadgar • Mazyar Khakpour Received: 4 November 2012 / Accepted: 29 April 2013 Ó Springer Science+Business Media New York 2013 Abstract A new strategy for the synthesis of thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles by an ionic-gelation method is presented. The synthetic approach was based on the utilization of 1,6-hexamethylene diiso- cyanate during cyclodextrin grafting onto carboxymethyl chitosan. The use of the 1,6-hexamethylene diisocyanate resulted in reactions between cyclodextrin and active sites at the C 6 -position of chitosan, and preserved amino groups of chitosan for subsequent reactions with thioglycolic acid, as the thiolating agent, and tripolyphosphate, as the gelling counterion. Various methods such as scanning electron microscopy, rheology and in vitro release studies were employed to exhibit significant features of the nanoparti- cles for mucosal albendazole delivery applications. It was found that the thiolated carboxymethyl chitosan-g-cyclo- dextrin nanoparticles prepared using an aqueous solution containing 1 wt% of tripolyphosphate and having 115.65 (lmol/g polymer) of grafted thiol groups show both the highest mucoadhesive properties and the highest albenda- zole entrapment efficiency. The latter was confirmed the- oretically by calculating the enthalpy of mixing of albendazole in the above thiolated chitosan polymer. 1 Introduction Hydrophobic drugs comprise a very important class of therapeutic agents which are of great potential use in treatment of cancer and helminth infections [1, 2]. Unfor- tunately, these pharmaceuticals have achieved limited success in clinical applications because of the difficulties in oral and intravenous administrations caused by low drug solubility in aqueous media, rapid hydrolysis and enzy- matic degradation. Several methods have been investigated to overcome these deficiencies, including the use of vari- ous drug carriers such as micelles [3], hydrogels [4, 5], microparticles [6, 7], nanoparticles [8, 9], etc. Among these drug delivery vehicles, the systems based on chitosan are of great interest due to their good biocompatibility, prolonged drug release behavior and non-toxicity [10–13]. Since, modification of chitosan, as a poor soluble and weakly interacting polysaccharide, is a critical prerequisite for its conjugation to hydrophobic drugs, considerable efforts have been devoted to address this issue in recent years. For Electronic supplementary material The online version of this article (doi:10.1007/s10856-013-4947-9) contains supplementary material, which is available to authorized users. G. Alamdarnejad Young Researchers Club, South Tehran Branch, Islamic Azad University, Tehran, Iran A. Sharif (&) Faculty of Chemical Engineering, Department of Polymer Engineering, Tarbiat Modares University, P.O. Box: 14155/143, Tehran, Iran e-mail: asharif@modares.ac.ir S. Taranejoo  M. Janmaleki Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran M. R. Kalaee Department of Polymer Engineering, Islamic Azad University, South Tehran Branch, Tehran, Iran M. Dadgar Faculty of Applied Chemistry, Islamic Azad University, South Tehran Branch, Tehran, Iran M. Khakpour Department of Polymer Engineering, Islamic Azad University, Kashan Branch, Kashan, Iran 123 J Mater Sci: Mater Med DOI 10.1007/s10856-013-4947-9