Elsevier

Carbohydrate Polymers

Volume 92, Issue 2, 15 February 2013, Pages 1357-1366
Carbohydrate Polymers

Hemicellulose-based pH-sensitive and biodegradable hydrogel for controlled drug delivery

https://doi.org/10.1016/j.carbpol.2012.10.032Get rights and content

Abstract

Hydrogels based on hemicellulose of wheat straw were prepared as a novel carrier for controlled drug delivery. The chemical structure and morphology of the hydrogels were characterised using FT-IR and SEM, respectively. The swelling ratios of the hydrogels were determined, and the results showed that the hydrogels were pH-responsive. The swelling kinetics of the hydrogels followed a Fickian diffusion process in media with a pH of 1.5, and water uptake was controlled collaboratively by hydrogel relaxation and water diffusion in media with pH values of 7.4 and 10.0. The degradation test of the hydrogels was conducted under simulated physiological conditions, and both hemicellulose content and the crosslinking density of the hydrogels were major factors that affected the biodegradability of the hemicellulose-based hydrogels. A comparison of the in vitro release of acetylsalicylic acid and theophylline indicated that the drug release was controlled both by the hydrogel and by the intrinsic character of the drug. According to the results presented here, hemicellulose-based hydrogels can be used in biomedical fields, especially for controlled drug release.

Highlights

Hemicelluloses isolated from wheat straw were employed to prepare pH-sensitive hydrogels. ► The swelling ratio of the hydrogel showed apparent transition at physiological pH. ► The swelling kinetics followed Fickian diffusion process in media of pH 1.5. ► The hemicelluloses content and crosslinking density affected the biodegradation. ► Drug release was controlled together by hydrogel and the intrinsic character of drug.

Introduction

In recent years, intelligent hydrogels have been widely studied because of their responsiveness to environmental stimuli, such as pH, ionic strength, solvent composition, temperature and electric and magnetic fields (Qiu & Park, 2001). Because of their special properties, hydrogels could be widely used in biomedical fields, including biological scaffolds for tissue engineering (Hoffman, 2002), biosensors, immobilised carriers for the encapsulation of living cells (Sefton, May, Lahooti, & Babensee, 2000), barrier materials to regulate biological adhesions (Bennett, Melanson, Torchiana, Wiseman, & Sawhney, 2003) and controlled delivery systems for drugs (Lin and Metters, 2006, Qiu and Park, 2001). pH-responsive hydrogels have received considerable attention in the field of oral drug delivery, not only because the hydrogels could protect the drug against acidic denaturation and reduce the noxious stimulation of drugs on the stomach, but also because they could prolong the residence time of drugs and reduce dosing frequency (Qiu & Park, 2001). Furthermore, because of the excellent biocompatibility and biodegradation of natural polymers, a variety of natural polysaccharides have been used to prepare hydrogels as harmless controlled release systems for drug delivery (Coviello et al., 2007, Lindblad et al., 2007).

Hemicellulose (HC), the second most abundant renewable natural polymer compared to cellulose, exists widely in plants. More and more attention has been concentrated on the development and application of hemicellulosic products because of their numerous inherent advantages, which include non-toxicity, biocompatibility, biodegradability and anti-cancer effect (Ebringerová et al., 2005, Oliveira et al., 2010). HC has been used as fermentation feedstock in the production of ethanol, butanol and xylitol (Ebringerová et al., 2005, Saha, 2003) and as raw materials in the preparation of food packaging films (Hansen and Plackett, 2008, Hartman et al., 2006). Xylan, the major HC isolated from grass and hardwood, has many beneficial effects, including anti-phlogistic effects, immune function (Ebringerová et al., 1998, Ebringerová et al., 2002), inhibitory action on the growth rate of tumours (Whistler, Bushway, Singh, Nakahara, & Tokuzen, 1976) and mutagenicity activity (Tsutomu, 1992). Some reports have noted that xylan was digested little in the physiological stomach environment but was consumed by anaerobic bacteria in the colon (Ebringerová and Heinze, 2000, Sinha and Kumria, 2001, Sinha et al., 2004, Yang et al., 2002). This unique property of xylan has advantages in the preparation of pH-responsive hydrogels for the controlled release of oral drugs.

Over the last decade, a few reports on the synthesis of HC-based hydrogels have appeared. Gabrielii et al. (Gabrielii and Gatenholm, 1998, Gabrielii et al., 2000) prepared a hydrogel by mixing HC (which contained glucuronic acid functional groups) with chitosan in acidic solution. Most of the studies on the synthesis of HC-based hydrogel focused on the introduction of alkenyl-functional groups onto the HC structure and their subsequent covalent cross-linking to form a hydrogel (Albertsson et al., 2010, Lindblad et al., 2005, Lindblad et al., 2001, Yang et al., 2011). In our study, a series of HC-based hydrogels were synthesised using various HC/acrylic acid monomer ratios (diverse neutralisation degree) and various amounts of initiator and crosslinker, to examine factors that affect the swelling behaviour and pH-sensitivity of the resulting hydrogels. The prepared hydrogels were characterised using scanning electronic microscopy (SEM), Fourier-transform infrared (FT-IR) spectrophotometry, and swelling tests. Degradation tests were conducted under simulated physiological conditions. Finally, an in vitro drug release study was performed using acetylsalicylic acid and theophylline as model drugs.

Section snippets

Materials

Wheat straw, from the Changan Region in the Shanxi Province of China, was ground to pass a 1 mm size screen, and HC was extracted from the wheat straw. Acrylic acid (AAc) was obtained from Shanghai Chemical Reagent Co. (China). Potassium persulfate, anhydrous sodium sulfite, and N,-N-methylene bisacrylamide (MBA) were purchased from Tianjin Fuchen Chemical Reagent Co. (China). Acetylsalicylic acid and theophylline as model drugs were provided by J&K Chemical (China branch). All chemicals used

Hemicellulose from wheat straw and synthesis of hydrogel

According to our previous study, the HC extracted from wheat straw in this study was mainly arabinoxylan (Sun, Sun, Fowler, & Baird, 2005). GC analysis showed that xylose was the major sugar in the isolated HC, comprising approximately 80.44% (w/w) of the total sugars, and arabinose (12.47%) was the second most abundant sugar. Glucose (4.28%) and galactose (2.81%) appeared as minor constituents, and mannose was not detected.

As illustrated in Scheme 2, the pH-sensitive hydrogels were synthesised

Conclusions

A novel pH-sensitive and biodegradable HC-based hydrogel was prepared by grafting AAc into HC. The swelling ratio showed apparent transitions at physiological pH. A porous honeycomb-like structure was clearly shown in the SEM images of the resulting hydrogels. The swelling kinetic experiments revealed that a Fickian diffusion process dominated the swelling of the hydrogels in media of pH 1.5 and that water uptake was controlled collaboratively by hydrogel relaxation and water diffusion in media

Acknowledgements

The authors thank for jointly supporting by the National Natural Science Foundation of China (No. 20707016), Shaanxi Science and Technology Research Project for Young Scientist (2012KJXX-10), and Fund for Fundamental Research of Northwestern Polytechnical University (NPU-FFR-JC20110274 and No. Z2012160).

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