Piperazine and its carboxylic acid derivatives-functionalized mesoporous silica as nanocarriers for gemcitabine: Adsorption and release study Zohreh Bahrami a , Alireza Badiei a,b, ⁎, Fatemeh Atyabi c , Hossein Reza Darabi d , Bita Mehravi e,f a School of Chemistry, College of Science, University of Tehran, Tehran, Iran b Nanobiomedicine Center of Excellence, Nanoscience and Nanotechnology Research Center, University of Tehran, Tehran, Iran c Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran d Chemistry and Chemical Engineering Research Center of Iran, Nano and Organic Synthesis Lab, Tehran, Iran e Celullar and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran f Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran abstract article info Article history: Received 1 September 2014 Received in revised form 30 October 2014 Accepted 17 December 2014 Available online 19 December 2014 Keywords: SBA-15 Nanorods Piperazine Carboxylic acid-functionalization Gemcitabine Cytotoxicity Piperazine-functionalized SBA-15 nanorods were synthesized by post grafting method with methyldimethoxysilylpropylpiperazine (MDSP). The carboxylic acid derivatives of piperazine-functionalized SBA-15 nanorods were obtained using two different kinds of precursors (bromoacetic acid and succinic anhy- dride). The prepared materials were used as nanocarriers for the anticancer drug (gemcitabine). The obtained samples were characterized by SAXS, N 2 adsorption-desorption, SEM, TEM, DLS, thermogravimetric analysis, FTIR, Raman and UV spectroscopies. The adsorption and release properties of all samples were investigated. In vitro study included cell toxicity. It was found that the surface functionalization increases the interaction be- tween the carrier and gemcitabine and results in the loading enhancement of the drug. In addition, the adsorp- tion of gemcitabine on the modified mesoporous matrix depends on the type of the introduced functional groups. The carboxylic acid-modified samples have higher loading content, due to the strong interaction with gemcitabine. The maximum content of deposited drug in the modified SBA-15 nanorods is close to 36 wt.% that it is related to PC2-SBA-15 sample which obtained using succinic anhydride. The obtained results reveal that the surface functionalization leads toward a significant decrease of the drug release rate without any appre- ciable cytotoxicity. No significant differences are observed among the drug release rate from the modified samples. © 2014 Elsevier B.V. All rights reserved. 1. Introduction Gemcitabine (Gem) is a water-soluble low-molecular-weight anti- cancer drug that is commonly used for the treatment of several kinds of cancers including colon, pancreatic, lung, breast, ovarian and bladder [1–3]. Gemcitabine passes through the cell membrane with difficulty and requires active transporters localized on the membrane to enter the cells [4,5]. Different drug delivery systems such as liposomes and polymeric nanoparticles were designed in order to protect Gem from rapid metabolization, overcome drug resistance, target drug delivery and improve its anticancer efficacy [6,7]. Since 2001, when MCM-41 was first proposed as a drug delivery sys- tem (DDS) [8], silica-based materials have been discussed as drug car- riers. Mesoporous silica nanoparticles (MSNs) possess several unique features such as high surface area, large pore volume, uniform and tunable pore sizes, excellent physicochemical stability, controllable morphology, modifiable surfaces, nontoxic nature and well biocompat- ibility [9–15]. These properties result in the study of application of MSNs in the biomedical field have attracted great attention. MSNs offer the possibility of lodging a variety of drug molecules such as, anti-inflammatory [8,16–20], antibiotic [11,21–23], antihypertensive [24], antiulcer [25,26], anti-osteoporotic [27] and anticancer [23]. It was demonstrated that surface functionalization [16,18,25,28], size and structure of pore [24,29–31], loading conditions [32] and chemical characteristics of the loaded drug [33] can affect both the ad- sorption and release of the drug into and out of MSNs. The chemical functionalization of the surface is essential because a mesoporous silica surface covered with silanol groups that are not selective enough to ad- sorb drug molecules with different functionalities [34,35]. In addition, it was shown that the attractive and repulsive electrostatic interactions between the entrapped molecules and the silica surface play an impor- tant role in the amount of adsorption of drug molecules and rate of their release. Therefore, the choice of appropriate functionalizing agent can enhance the adsorption capacity of drug and it should also allow modu- lating its release [35–39]. For example, the modification of MSNs with Materials Science and Engineering C 49 (2015) 66–74 ⁎ Corresponding author at: School of Chemistry, College of Science, University of Tehran, Tehran, Iran. E-mail address: abadiei@khayam.ut.ac.ir (A. Badiei). http://dx.doi.org/10.1016/j.msec.2014.12.069 0928-4931/© 2014 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Materials Science and Engineering C journal homepage: www.elsevier.com/locate/msec