Structural analysis of dextrins and characterization of dextrin-based biomedical hydrogels
Introduction
Dextrins are a class of low molecular weight carbohydrates produced by acid or/and enzymatic partial hydrolysis of starch or glycogen, thus exhibiting the α-(1 → 4)-Glc structure of amylose and the α-(1 → 4)- and α-(1 → 4,6)-Glc branched structure of amylopectin, but with lower polymerization. The extent of hydrolysis is expressed in terms of “dextrose equivalent” (DE), a measure of the total reducing power (Chronakis, 1998, White et al., 2003). Dextrins with the same DE can display differences in terms of hygroscopicity, fermentability, viscosity, sweetness, stability, gelation, solubility, and bioavailability, which may be assigned to distinct structural features (Chronakis, 1998). Depending on the source of the native starch, as well as on the hydrolysis conditions, several types of dextrins can be obtained, displaying different properties that can be suited for specific applications.
Dextrins are an affordable raw material, generally regarded as safe (GRAS) (Alvani, Qi, & Tester, 2011). It is a widely used material with a great variety of applications such as adhesives, foods, textiles and cosmetics (Gonçalves, Moreira, Carvalho, Silva, & Gama, 2014). Regarding biomedical applications, dextrin is yet relatively unexplored, being clinically used as a peritoneal dialysis solution that can also perform as a drug delivery solution (Peers and Gokal, 1998, Takatori et al., 2011) and as wound dressing agent (DeBusk & Alleman, 2006). Although its limited number of current biomedical applications, dextrin exhibit a set of advantages that potentiates its use specifically in the biomaterials field. It is a biocompatible and non-immunogenic material, degradable in vivo by α-amylases and its molecular weight ensures renal elimination avoiding tissue accumulation due to repeated administration (Hreczuk-Hirst et al., 2001, Moreira et al., 2010).
Hydrogels are three-dimensional, hydrophilic and polymeric networks that are highly hydrated and are receiving attention as scaffold materials (Drury and Mooney, 2003, Hoffman, 2002). The relevance of injectable hydrogels for biomedical purposes has increased in the last years since they generally are biocompatible, biodegradable, exhibit mechanical and structural properties that resembles extracellular matrix, are processed under mild conditions and enable less invasive clinical procedures (Drury and Mooney, 2003, Hoffman, 2002, Van Vlierberghe et al., 2011). Hydrogels can be used alone or in combination with other components (e.g. cells, drugs, DNA, signalling molecules) (Jagur-Grodzinski, 2010, Peppas et al., 2006).
Several dextrin-based hydrogels, obtained by radical polymerization have been reported (Carvalho et al., 2007, Carvalho et al., 2009, Das et al., 2013, Das et al., 2014, Moreira et al., 2010). Also, an oxidized dextrin hydrogel cross-linked with adipic acid dihydrazide was described by our group (Molinos, Carvalho, Silva, & Gama, 2012). Adipic acid dihydrazide may be used to promote the reticulation of polysacharide-based hydrogels, such as oxidized dextran (Maia, Ferreira, Carvalho, Ramos, & Gil, 2005), hyaluronic acid (Schramm et al., 2012);(Su, Chen, & Lin, 2010), poly(aldehyde guluronate) (Bouhadir, Hausman, & Mooney, 1999), among others. Despite the overall good biocompatibility, Schramm et al. (2012) reported a mild cytotoxic effect of the dihydrazide-reticulated hydrogels. However, information about the biocompatibility of non-crosslinked monomer is very scarce. This work provides a comprehensive structural characterization of several commercial dextrins, which were used to produce oxidized dextrin hydrogels reticulated with adipic acid dihydrazide. The cytotoxicity of the crosslinking agent was evaluated and compared with that of glutaraldehyde. The later is a widely used crosslinker, often considered cytotoxic (Huang-Lee et al., 1990, Mcpherson et al., 1986), but still used for reticulation of biomedical products (Furst & Banerjee, 2005).
Section snippets
Materials
All reagents used were of laboratory grade and purchased from Sigma-Aldrich, unless stated otherwise. Koldex 60 dextrin was a gift from Tate & Lyle. Tackidex was a gift from Roquette. Dextrins w28, w35, w60 and w80 were a gift from Avebe. Icodextrin and D4894 were obtained from Baxter and Sigma, respectively. All other chemicals and solvents used in this work were of the highest purity commercially available.
Structural analysis of dextrins
Neutral sugars were determined as alditol acetates as described by Nunes et al. (2012).
Structural dextrin analysis
The dextrins used in this work are commercially available products. These materials are not sufficiently characterized, and as it will be shown, some of the available information is equivocal. In this work, we aimed at correlating the dextrin's structural differences with the properties of the derived hydrogels. All dextrin's analysed were composed only by glucose, as confirmed by sugar methylation analysis, which revealed the presence of (1 → 4)-, terminally-, and (1 → 4,6)-linked Glcp residues in
Conclusions
The structural characterization showed that dextrins from different sources displayed structural differences, namely regarding chain length and branching degree. The molecular weight of dextrins is much lower than the values often reported in the literature, commonly obtained by SEC. However, these differences do not seem to influence the gelation and degradation of the hydrogels. The combination with a dextrin nanogel and urinary bladder matrix was successfully achieved. The cytotoxicity of
Acknowledgments
D.M.S. was supported by the grant SFRH/BD/64571/2009 from Fundação para a Ciência e Tecnologia (FCT), Portugal. We thank FCT funding through EuroNanoMed ENMED/0002/2010. The authors acknowledge the funding from QREN (“Quadro de Referência Estratégica Nacional”) and ADI (“Agência de Inovação”) through the project Norte-07-0202-FEDER-038853.
QOPNA research unit is funded by Fundação para a Ciência e a Tecnologia (FCT, Portugal, European Union, QREN, FEDER, and COMPETE (project
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- 1
Contributed equally to this study.