Hydrogels prepared by graft copolymerization of chitosan and N-isopropylacrylamide via g-radiation. Effects of monomer concentration and irradiation dose on grafting percentage and grafting efficiency were studied. PH and thermosensitivity and swelling properties of the hydrogels were investigated.
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Original Title
Synthesis and Characterization of Temp and PH- Sensitive Hydrogels Based on Chitosan-grafted NIPAAm Radiation
Hydrogels prepared by graft copolymerization of chitosan and N-isopropylacrylamide via g-radiation. Effects of monomer concentration and irradiation dose on grafting percentage and grafting efficiency were studied. PH and thermosensitivity and swelling properties of the hydrogels were investigated.
Hydrogels prepared by graft copolymerization of chitosan and N-isopropylacrylamide via g-radiation. Effects of monomer concentration and irradiation dose on grafting percentage and grafting efficiency were studied. PH and thermosensitivity and swelling properties of the hydrogels were investigated.
Synthesis and characterization of thermo- and pH- sensitive
hydrogels based on Chitosan-grafted N-isopropylacrylamide via g-radiation Hong Cai a , Zheng Pu Zhang a, , Ping Chuan Sun a , Bing Lin He a , Xiao Xia Zhu a,b a State Key Laboratory of Functional Polymeric Materials for Adsorption and Separation, Tianjin, 300071, China b Departement de chimie, Universite de Montreal, C.P. 6128, Succursale Centre-ville, Montreal, QC, Canada H3C 3J7 Received 30 September 2004; accepted 12 October 2004 Abstract Thermo- and pH-sensitive hydrogels were prepared by graft copolymerization of chitosan (CS) and N- isopropylacrylamide via g-radiation. The effects of monomer concentration and irradiation dose on grafting percentage and grafting efciency were studied. The graft copolymers were characterized by 13 C CP/MAS NMR and thermogravimetric analysis. The pH and thermosensitivity and swelling properties of the hydrogels were investigated. The results showed that the grafting percentage and grafting efciency increased with the increase of monomer concentration and total irradiation dose. The highest grafting percentage is 620%, the lower critical solution temperature (LCST) of this hydrogel is about 28 1C. r 2004 Elsevier Ltd. All rights reserved. Keywords: Chitosan; N-isopropylacrylamide; Thermo- and pH-sensitive; Graft; g-radiation 1. Introduction Hydrogels are crosslinked, three-dimensional hydro- philic polymer networks, which swell but do not dissolve when brought into contact with water. Some hydrogels, which sometimes undergo a volume change in response to a change in surrounding conditions such as tempera- ture (Hirokawa and Tanaka, 1984; Bae et al., 1990; Zhang et al., 2002), pH (Park and Hoffman, 1992; Guan et al., 1996; Chen and Hoffman, 1995), antigen (Miyata et al., 1999), light (Suzuki and Tanaka, 1990) and certain chemicals (Ishihara et al., 1984; Kokufata and Zhang, 1991; Holtz and Asher, 1997), etc. Poly-N-isopropyla- crylamide (PNIPA) is the most widely studied thermo- sensitive hydrogels. PNIPA in aqueous medium has its lower critical solution temperature (LCST) at 32 1C. The volume phase transition is reversible, which led to some potential applications such as temperature sensors, controlled drug-releasing devices, articial muscles, and enzyme-activity control (Fang and Kawaguchi, 2002; Kurisawa et al., 2000; Bae et al., 1987; Liu et al., 1993). Chitosan (CS) is a natural cationic polymer obtained from N-deacetylation of chitin [(14)-2-acetamiodo-2- deoxy-d-glucose], which is the second most abundant natural polymer on earth after cellulose. This poly- saccharide is considered to be nontoxic, biodegradable, ARTICLE IN PRESS www.elsevier.com/locate/radphyschem 0969-806X/$ - see front matter r 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.radphyschem.2004.10.007
Corresponding author. Tel.: +86 22 23505046;
fax: +86 22 23503510. E-mail address: zhangzp@nankai.edu.cn (Z.P. Zhang). and biocompatible. O HOH 2 C NH 2 HO O n 1 2 3 4 5 6 Chitosan It has been used as an anticoagulant, a wound-healing accelerator, and drug delivery material (Caner et al., 1998; Singh and Ray, 1994; Mima et al., 1983). CS exhibits a pH-sensitive behavior as a weak polybase due to the large quantities of amino groups on its chain. Graft copolymerization of vinyl monomers onto CS can introduce desirable properties and enlarge the eld of the potential applications by choosing various types of side chains (Kumbar and Aminabhavi, 2003; Shantha and Harding, 2002.; Wang et al., 2000; Kim et al., 2000). In recent years, a number of initiator systems have been developed to initiate grafting copolymerization. Radiation graft copolymerization is a well-established technique for producing polymeric materials that combine the chemical and physical properties of both the base polymer and the grafted monomer (Singh and Ray, 1997; Zhai et al., 2000; Li et al., 2003). In this work, hydrogels based on CS grafted N-isopropylacrylamide were prepared by 60 Co g-radia- tion, the effects of monomer concentration and irra- diation dose on grafting percentage and grafting efciency were studied. The pH- and thermosensitivity and swelling properties of the polymers were also investigated. 2. Experimental 2.1. Materials CS was purchased from Qingdao Lizhong Chitosan Co., Ltd. China. The viscosity-average molecular weight was 97000 g/mol and the N-deacetylation degree was 85%. NIPA was synthesized by reacting acryloyl chloride with isopropylamine. All other chemicals were of analytical grade and were used without further purication. 2.2. Graft polymerization A series of CS-g-NIPA hydrogels were prepared in the following procedures: pure CS (0.5 g) dissolved in 5% aqueous acetic acid (25 ml) in a glass reaction bottle, the monomer was added to the CS solution. Mohrs salt (ammonium ferrous sulphate) was added to the mixture to minimize homopolymerization during irradiation. The solution was deoxygenated by purging with nitro- gen for 30 mins. The sealed reaction bottles were irradiated at a dose from 3 to 10 kGy. After irradiation, the product was extracted with methanol in a Soxhlet extractor for 48 h, in order to remove the unreacted monomer, homopolymer and other impurities. The hydrogel was dried at 40 1C in a vacuum oven overnight. The grafting percentage (G %) and grafting efciency (GE %) were dened as follows: G% W g W o =W o 100; GE% W g W o =W m 100; where W g , W o and W m are the weights of grafted copolymer, chitosan and monomer, respectively. 2.3. Characterization 2.3.1. 13 C CP/MAS NMR analysis 13 C CP/MAS NMR spectra were recorded on a Varian UNITY plus 400 NMR spectrometer in solid state at a frequency of 100.6 MHz for 13 C nuclei. Sample was placed in a zirconia rotor (5 mm), the spinning rate was set at 4.5 kHz at the magic angle, and 13 C chemical shifts were referenced to external hexamethylbenzene. 2.3.2. Thermogravimetric analysis Dynamic thermogravimetric analysis was carried out with a NETZSCH TG209 thermogravimetric analyzer from Germany. The experiments were performed at a heating rate of 10 1C/min from room temperature to 600 1C. 2.3.3. Swelling measurement Swelling of the hydrogel was determined gravimetri- cally after immersing the grafted product in water for a week, the surface of the hydrogel was wiped with lter paper in order to remove the free water and weighed. The swelling ratio was determined as Swelling ratio W s =W d ; where W s and W d are the weights of swollen and dry hydrogels, respectively. 2.3.4. Thermal and pH analysis The hydrogel was ground to powder, passed through a sieve of 100 mesh, immersed in water for a week. The thermosensitivity was measured by turbidimetry ob- served at l 500 nm at different temperatures. The hydrogels were immersed in the buffers of various pH values from 1 to 13 for a week. The pH sensitivity was measured by swelling ratios in different pH buffers. ARTICLE IN PRESS H. Cai et al. / Radiation Physics and Chemistry 74 (2005) 2630 27 3. Result and discussion 3.1. Grafting characterization 3.1.1. Gravimetric estimation The graft copolymerization was monitored gravime- trically. After the extraction of the homopolymer, the weight gain of CS gives strong evidence for the grafting of NIPA onto CS. 3.1.2. 13 C CP/MAS NMR spectroscopy analysis 13 C CP/MAS NMR spectra of CS and grafted CS were shown in Fig. 1. The peak assignments of 13 C chemical shifts of CS were 53.4 (C2), 56.8(C6), 71.4 (C3, 5), 79.2 (C4), and 101.6 (C1) ppm respectively, which is close to the previous NMR experimental result of CS (Yoksan et al., 2001). Except for the signals of CS denoted as c in Fig. 1, several new peaks denoted as d in Fig. 1 were found at a range from 1045 ppm in grafted CS, which should be assigned to aliphatic signals of grafted PNIPA, this further conrms the grafting of PNIPA onto CS. On the other hand, it is known that CS molecule contains two reactive groups at C2 and C6 positions (Liu et al., 2001). The grafted CS showed downeld shifts for both, which implies that the grafting reaction may have taken placed on C2 and C6 positions. In addition, we also noticed that all peaks in the grafted CS were broadened as the result of the paramagnetic effect of Fe 3+ of ammonium ferrous sulphate on the 13 C NMR signals. 3.1.3. Thermogravimetric analysis The thermograms of CS and grafted CS (PG 620%) obtained at a heating rate of 10 1C/min under nitrogen are shown in Fig. 2. The thermogram of CS exhibits two distinct stages. One is in the range of 40120 1C due to water loss and decomposition of polymers of low molecular weights, the other in the range of 220480 1C is ascribed to a complex process including dehydration of the sugar rings, depolymerization and decomposition of the acetylated and deacetylated units of the polymer. The differential thermogravimatric curve of the grafted CS shows three degradation steps. For the grafted CS, the second degradation stage starts at about 210 1C which is lower than that of CS. In the third stage of degradation in the range of 370480 1C, the grafted CS degrades faster than that of CS. The appearance of this stage indicates the structure of CS chains has been changed due to the grafting of NIPA chains. 3.2. Effects of monomer concentration and irradiation dose Fig. 3 gives the variation in grafting percentage and grafting efciency with monomer concentration. ARTICLE IN PRESS 160 140 120 100 80 60 40 20 0 -20 (b) (a) (c) C1 C4 C3,5 C2,6 (d) ppm Fig. 1. 13 C-NMR spectra of (a) CS and (b) CS-g-NIPA. 0 200 400 600 800 20 40 60 80 100 (b) (a) T G % Temperature (C) Fig. 2. TGA curves of (a) CS and (b) CS-g-NIPA. 1:1 1:3 1:5 1:7 0 100 200 300 400 500 600 700 G ( % )
0 20 40 60 80 100 G E ( % ) 1:9 CS/NIPA (mol/mol) Fig. 3. The effect of monomer concentration on the degree of grafting and grafting efciency. H. Cai et al. / Radiation Physics and Chemistry 74 (2005) 2630 28 Grafting was carried out at room temperature at a dose of 10 kGy. The results showed that there is an increase in the grafting percentage and grafting efciency with increasing monomer concentration. During the grafting process, the monomers continuously diffused into the polymer. The ability of CS macroradicals to capture NIPA depends on the availability of NIPA molecules in their vicinity. Therefore, the increase in monomer concentration leads to an increase in grafting percentage and grafting efciency. The effect of total irradiation dose on grafting percentage and grafting efciency is presented in Fig. 4. The graph exhibited an increase in grafting percentage and grafting efciency with the increase in the dose range from 3 to 10 kGy. The increase of grafting percentage and grafting efciency may be due to the increasing concentration of free radicals formed in the polymer substrate. 3.3. Swelling studies The effect of grafting percentage on the swelling ratios for the hydrogels at room temperature is shown in Fig. 5. It can be seen an increase in the swelling ratios with the increase of grafting percentage. Clearly, the swelling behavior of the hydrogels depends on the amount of the grafted branches. 3.4. Thermal and pH analysis The thermosensitivity of the hydrogels is shown in Fig. 6, measured by the transparency of the hydrogels under different temperature. There is a sharp decrease in the transparency when the temperature is about 28 1C, the LCST of the grafted hydrogels (620% grafting percentage). The swelling ratios for hydrogels in different pH solutions shown in Fig. 7 indicate that the swelling ratios ARTICLE IN PRESS 2 4 6 8 10 0 20 40 60 80 100 120 140 160 G ( % ) 10 20 30 40 50 60 70 80 G E ( % ) Irradiation Dose (KGy) Fig. 4. The effect of irradiation dose on the degree of grafting and grafting efciency. 100 200 300 400 500 600 700 4 6 8 10 12 14 16 18 20 22 S w e l l i n g
r a t i o Grafting Percentage(%) Fig. 5. Swelling ratio as a function of grafting percentage. 20 25 30 35 40 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10 T % t(C) Fig. 6. Light transmission as a function of temperature (l 500 nm). 0 2 4 6 8 10 12 14 0 5 10 15 20 25 S w e l l i n g
r a t i o pH Fig. 7. Effect of pH on swelling ratios. H. Cai et al. / Radiation Physics and Chemistry 74 (2005) 2630 29 decrease with the increase of pH value of the buffer solutions. This is because PNIPA gels do not have pH sensitivity in the buffer solution but CS has. 4. Conclusion NIPA was successfully grafted onto CS by g-radiation induced technology for the rst time. The grafting percentage and grafting efciency can be controlled by appropriate selection of grafting conditions, such as monomer concentration and total irradiation dose. The CS-g-NIPA hydrogels showed good thermo- and pH- sensitivity and swelling property. Acknowledgments The authors are grateful to the CRC program of Canada Mr. Yangeng Zhang of the Tianjin Institute of Technological Physics for providing the radiation source and helpful advice. References Bae, Y.H., Okano, T., Hsu, R., Kim, S.W., 1987. Thermo- sensitive polymers as onoff switches for drug release. Makromol. Chem. Rapid. Commun. 8, 481485. 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