Carbohydrate Polymers 155 (2017) 303–312 Contents lists available at ScienceDirect Carbohydrate Polymers journal homepage: www.elsevier.com/locate/carbpol Radiation grafting of N-vinylcaprolactam onto nano and macrogels of chitosan: Synthesis and characterization Angélica Cruz a , Lorena García-Uriostegui b , Alejandra Ortega a , Takashi Isoshima c , Guillermina Burillo a,∗ a Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, Ciudad Universitaria, México 04510, D.F., Mexico b CONACYT Research Fellow at Departamento de Madera Celulosa y Papel-Universidad de Guadalajara, Carretera Guadalajara-Nogales Km. 15.5, Zapopan, Jalisco 45110, Mexico c Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan a r t i c l e i n f o Article history: Received 7 June 2016 Received in revised form 24 August 2016 Accepted 26 August 2016 Available online 29 August 2016 Keywords: N-vinylcaprolactam Chitosan grafting Nanogels of chitosan Radiation grafting a b s t r a c t The aim of this study was to synthesize chitosan hydrogels, in macro- and nano-size, grafted with N- vinylcaprolactam (NVCL) using gamma radiation, and evaluate their potential application as a drug delivery system, using 5-fluorouracil (5-FU) as a model drug. The effect of dose and monomer concen- tration in the grafting process was studied, and the materials were characterized by FTIR, TGA, DLS, SEM and AFM. Higher grafting percentages were observed for the nanogels system. Although both the grafted macro- and nanogels, (net-CS)-g-NVCL, showed a response to pH (4.75) and temperature (31–33 ◦ C), the nanogels showed a better swelling response to both stimuli because of their higher surface area. Both sys- tems were able to load 5-FU in small amounts (2–3.5 mg g −1 ) and the release was sustained for more than 12 h, showing that the modified macro and nanogels can be a potential alternative for the administration of drugs. © 2016 Published by Elsevier Ltd. 1. Introduction Chitosan (CS) is a linear polysaccharide composed of randomly distributed -(1–4)-linked d-glucosamine (deacetylated unit) and N-acetyl d-glucosamine (acetylated unit). As a polysaccharide, CS exhibits attractive properties such as biocompatibility and biodegradability (Kumar, 2000), and thus it is extensively used in the pharmaceutics, cosmetics, biomedical, agriculture, biotechno- logical, paper, and textile fields (Mourya & Inamdar, 2008), as well as in water treatment. In addition, its degradation products are non-toxic, non-immunogenic and non-carcinogenic, so CS has also been found to be a good candidate as a supporting material for gene delivery, cell culture, and gene tissue engineering. Through the use of graft copolymerization, CS can be endowed with new desired properties that will enlarge its potential applications in the drug delivery, tissue engineering, antibacterial, biomedical, and dye removal fields (Chmielewski, 2010; Majeti & Kumar, 2000). In this regard, poly(N-vinylcaprolactam), PNVCL, is a non-ionic, ∗ Corresponding author. E-mail address: burillo@nucleares.unam.mx (G. Burillo). biocompatible, thermoresponsive polymer, that is water soluble at room temperature, and has a lower critical solution temperature (LCST) in the 32 − 35 ◦ C temperature range, which is near physiolog- ical temperature. Moreover, PNVCL has a relatively high resistance to hydrolysis and it does not produce toxic amide compounds (Vihola, Laukkanen, Valtola, Tenhu, & Hirvonen, 2005), making it attractive for biomedical and pharmaceutical applications (De las Heras, Pennadam, & Alexander, 2005 ; Zdyrko, Klep, & Luzinov, 2003). Hydrogels can be size-tuned into macroscopic networks, or into gels with smaller dimensions such as microgels. When the size of microgels is in the submicron range, they are known as nanogels. Some of the features of using microgels and nanogels for biomedical purposes are that they offer a large surface area for mul- tivalent conjugation, and they have an interior network that can be used for the incorporation/retention of bioactive molecules such as drugs, proteins, carbohydrates, and DNA (Oh, Drumright, Siegwart, & Matyjaszewski, 2008). In addition, compared with CS macro- gels and microgels, the adsorption performance could be greatly improved with nanogels (Jia, Yujun, & Guangsheng, 2005). When it comes to drug delivery vehicles, nanoparticles, which can be com- posed of natural or artificial polymers ranging in size between 10 http://dx.doi.org/10.1016/j.carbpol.2016.08.083 0144-8617/© 2016 Published by Elsevier Ltd.