Dextran Hydrogels Research Articles

Synthesis, characterization of dextran hydrogels and their in vitro release of gentamycin sulphate.

This study reports on the synthesis and characterization of biodegradable dextran-allyl isocyanate-ethylamine (Dex-AE)/polyethylene glycol-diacrylate (PEGDA) hydrogels for the controlled release of gentamycin sulphate (GS) and in vitro inhibition of organisms. The Dex-AE precursor was prepared through a 2-step chemical modification and characterized by Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) results revealed that an increase in Dex-AE content led to an initial decrease in pore size of the Dex-AE/PEGDA hydrogels, but a further increase in Dex-AE content resulted in a slightly increase of pore size. The swelling data indicated that the swelling ratio depended on the precursor feed ratio. GS was incorporated into the hydrogels through 2 different methods, i.e., immersed and crosslinked. The crosslinked GS-Dex-AE/PEGDA hydorgels exhibited stronger antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Finally, the viscoelastic properties of crosslinked GS-Dex-AE/PEGDA hydorgels were investigated.

Effect of 70-kDa and 148-kDa dextran hydrogels on praziquantel solubility

Praziquantel is an anthelmintic widely used in the treatment of schistosomiasis. Although a highly permeable drug, praziquantel is poorly soluble in water, limiting its bioavailability. Improving the solubility of poorly water-soluble drugs has become an important issue for analysis in pharmaceutical research. The use of dextran hydrogels is an advantageous strategy and the focus of extensive research. In this study, several hydrogels were developed from homologous polymer blends using 70 and 148 kDa dextrans in different proportions containing praziquantel, with the aim of evaluating the effects of polymeric release systems on the solubility of poorly water-soluble drugs such as praziquantel. Nine formulations were prepared, and the solubility of the drug incorporated was assessed. Three of the formations were selected to be characterized by DSC for the study in order to gain a better understanding of the thermal behavior of praziquantel incorporated into dextran hydrogels and the influence of polymers on the solubility of the drug, complemented by XRD and SEM techniques. According to the results, formation of crystallites of praziquantel occurred, probably due to the preparation procedures of the formulations, covering the surface of the polymer matrix and promoting a slight improvement in solubility. These data show that the use of hydrogels for the purposes of improving the solubility of poorly water-soluble drugs represents an effective strategy.

Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs

Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.

Cinnamate of inulin as a vehicle for delivery of colonic drugs

Colon diseases are difficult to treat because oral administrated drugs are absorbed at the stomach and intestine levels and they do not reach colon; in addition, intravenous administrated drugs are eliminated from the body before reaching colon. Inulin is a naturally occurring polysaccharide found in many plants. It consists of β 2-1 linked d-fructose molecules having a glucosyl unit at the reducing end. Various inulin and dextran hydrogels have been developed that serve as potential carrier for introduction of drugs into the colon. Because inulin is not absorbed in the stomach or in the small intestine, and inulin is degraded by colonic bacteria, drugs encapsulated in inulin-coated vesicles could be specifically liberated in the colon. Therefore, the use of inulin-coated vesicles could represent an advance for the treatment of colon diseases. Here, we study the use of a cinnamoylated derivative of chicory inulin as a vehicle for the controlled delivery of colonic drugs. The encapsulation of methotrexate in inulin vesicles and its release and activity was studied in colon cancer cells in cultures.

Spatial control of cell gene expression by siRNA gradients in biodegradable hydrogels.

The extracellular environment exposes cells to numerous biochemical and physical signals that regulate their behavior. Strategies for generating continuous gradients of signals in biomaterials may allow for spatial control and patterning of cell behavior, and ultimately aid in the engineering of complex tissues. Short interfering RNA (siRNA) can regulate gene expression by silencing specific mRNA molecules post-transcriptionally, which may be valuable when presented in a continuous gradient for regenerative or therapeutic applications. Here, a biodegradable hydrogel system containing a gradient of siRNA is presented, and its capacity to regulate protein expression of encapsulated cells in a spatially continuous manner is demonstrated. Photocross-linkable dextran hydrogels containing a gradient of siRNA have been successfully fabricated using a dual-programmable syringe pump system, and differential gene silencing in incorporated cells that is sustained over time has been shown using green fluorescent protein as a reporter. This platform technology may be applied in tissue engineering to spatially control biologically relevant cellular processes.

Composite pullulan–dextran polysaccharide scaffold with interfacial polyelectrolyte complexation fibers: A platform with enhanced cell interaction and spatial distribution

Hydrogels are highly preferred in soft tissue engineering because they recapitulate the hydrated extracellular matrix. Naturally derived polysaccharides, like pullulan and dextran, are attractive materials with which to form hydrophilic polymeric networks due to their non-immunogenic and non-antigenic properties. However, their inherent hydrophilicity prevents adherent cell growth. In this study, we modified pullulan–dextran scaffolds with interfacial polyelectrolyte complexation (IPC) fibers to improve their ability to support adherent cell growth. We showed that the pullulan–dextran–IPC fiber composite scaffold laden with extracellular matrix protein has improved cell adhesion and proliferation compared to the plain polysaccharide scaffold. We also demonstrated the zero-order release kinetics of the biologics bovine serum albumin and vascular endothelial growth factor (VEGF) incorporated in the composite scaffold. Lastly, we showed that the VEGF released from the composite scaffold retained its capacity to stimulate endothelial cell growth. The incorporation of IPC fibers in the pullulan–dextran hydrogel scaffold improved its functionality and biological activity, thus enhancing its potential in tissue engineering applications.

Injectable, in situ gelling, cyclodextrin-dextran hydrogels for the partitioning-driven release of hydrophobic drugs.

Injectable, degradable hydrogels based on cross-linking between aldehyde-functionalized dextran, hydrazide-functionalized dextran, and hydrazide-functionalized beta-cyclodextrin (βCD) were developed for hydrophobic drug delivery. βCD functions as both the in situ-gelling agent driving hydrogel formation as well as the binding site for the hydrophobic model drug, dexamethasone. In hydrogel systems where βCD is primarily covalently attached to the polymer network through cross-linking, the amount of drug release per sampling point is independent of the time between samples, the solubility of drug in the release medium, and the cross-link density of the hydrogel; instead, drug release is controlled primarily by partitioning of free (water-solubilized) drug between the hydrogel and the release medium. When the concentration of the hydrazide-functionalized dextran polymer was increased and more hydrazide groups were available to compete with βCD reactive sites for cross-linking the polymers, greater than ten-fold more drug was released from the hydrogel during the 20 day sampling period. Mobile, non-cross-linked βCD increases the solubility of the drug and facilitates rapid drug release by diffusion, as confirmed by quenching βCD-bound hydrazide groups. In this way, via a very subtle change in the composition of the injectable hydrogel, both the kinetics of drug release as well as the mechanism of drug release can be tuned over a wide range. Together with the low cytotoxicity of the materials, these results suggest that injectable βCD-based hydrogels have potential for facilitating controlled release of hydrophobic drugs over multiple time scales by controlling the mobility of βCD within the hydrogel network.

Strong Collagen Hydrogels by Oxidized Dextran Modification

Collagen hydrogel has been regarded as an excellent biomaterial because it is an abundant and sustainable resource and has good biocompatibility and controllable cell-based biodegradability. However, the poor mechanical properties of collagen hydrogel are the main disadvantage preventing it from having wide applications. In this communication, we use aldehyde-functionalized dextran, which is prepared from the oxidation of another natural polymer dextran, as a macromolecular cross-linker to enhance the strength of the collagen hydrogel. The resulting collagen/aldehyde-functionalized dextran (Col/DAD) hydrogels are much stronger and show better thermostability than the pristine collagen hydrogel, as expected. The maximum compressive strength of the Col/DAD hydrogel is 32.5 ± 1.6 kPa, which is about 20 times more than that of the pristine collagen hydrogel. We also prove that our method maintains the good biocompatibility of the collagen hydrogel and does not bring the cytotoxicity often observed from conven...

Thiolated human serum albumin cross-linked dextran hydrogels as a macroscale delivery system

Hydrogels play an important role in macroscale delivery systems by enabling the transport of cells and molecules. Here we present a facile and benign method to prepare a dextran-based hydrogel (Dex-sHSA) using human serum albumin (HSA) as a simultaneous drug carrier and covalent cross-linker. Drug binding affinity of the albumin protein was conserved in the thiolation step using 2-iminothiolane and subsequently, in the in situ gelation step. Oscillation rheometry studies confirmed the formation of a three-dimensional viscoelastic network upon reaction of dextran and the HSA protein. The mechanical properties of Dex-sHSA hydrogel can be tuned by the protein concentration, and the degree of thiolation of sHSA. Sustained release of hydrophobic drugs, such as ibuprofen, paclitaxel and dexamethasone, from the Dex-sHSA network was shown over one week. Hence, this albumin-based dextran hydrogel system demonstrates its potential as a macroscale delivery system of hydrophobic therapeutics for a wide range of biomedical applications.

Molecular dynamics simulations on dextran hydrogels

Abstract To probe the detailed structure of dextran hydrogels, periodical models for three dextran hydrogel systems with different dextran contents have been constructed and compared using molecular dynamic simulations. The software packages of Amorphous and Discover in Material Studio with COMPASS force field were used for the simulation. Energy minimization and geometry optimization were used to refine the models. In particular, the structure and dynamic movement of dextran chains which impose on water in the dextran hydrogel systems have been studied. The results show that in the physically crosslinked dextran hydrogels, KCl served as the crosslinker and it interacted with dextran via the oxygen atoms of hydroxyl groups in dextran ring. With increasing dextran content, the free volumes of the hydrogels and the diffusion coefficients of water in the hydrogel decrease. By the radial distribution analysis, the water in the hydrogel networks was found to interact with dextran via hydrogen bond and there are at least three kinds of water in the physically crosslinked dextran hydrogels. These results have a great significance for understanding the structure and properties of the hydrogel.

Microscale enzyme reactors comprising gold nanoparticles with immobilized trypsin for efficient protein digestion

Microscale sample processing devices for application in bioanalysis and proteome related studies have undergone rapid advancements during the recent years. Several techniques for the preparation of chip-based and capillary-based microfluidic systems and their modification with desired functionalities have been reported. The use of microfluidic devices allow easy processing of extremely small sample quantities with low reagent consumption and offer high surface areas and surface-to-volume ratios. Microscale sample processing devices find application in various research fields such as chemical analysis, kinetic studies, and bioanalytical research. In MS-based proteomics, enzymatic digestion is one of the key steps in the identification of proteins and their posttranslational modifications. However, this is usually the slowest step in the analysis workflow. Thus, the development of suitable devices and methods capable of performing efficient protein digestion more rapidly has become an area of considerable interest. The immobilization of proteolytic enzymes on different kinds of stationary phases, such as monoliths, microparticles and nanoparticles and inner surface of sample transfer capillaries has shown promising results. On the other hand, problems associated with the fabrication and applicability of different stationary phases may pose some challenges, such as monolithic supports involve time consuming fabrication procedures. Similarly, particle-based supports usually involve multistep synthesis and require extended incubation times for protein digestion. Hence, in order to accelerate digestion, other techniques such as microwave irradiation have been employed, which will further complicate the experimental setup. Alternatively, open channel microreactors comprising immobilized enzymes have appeared as a promising alternative, offering minimal restriction over the flow rates. Krenkova et al. prepared open tubular enzyme-immobilized reactors by coupling of trypsin and pepsin to the inner wall of a fused silica capillary. Stigter et al. reported the development of an open tubular trypsin reactor based on amino-modified and carboxyl-modified dextran. Later, the same group prepared a pepsin-immobilized reactor in a dextran-modified fused silica capillary for online protein digestion. The coating of the capillary wall with dextran hydrogel was carried out in order to load higher amounts

Cationic amphiphilic dextran hydrogels with potential biomedical applications

Dextran microparticles were chemically modified for the attachment of quaternary ammonium groups carrying substituents with different hydrophobicity, in order to obtain amphiphilic cationic hydrogels with different hydrophilic/lipophilic balance. These hydrogels retain various amounts of dyes: Rose Bengal, Brilliant Blue and Vitamin B12, used as models for hydrophobic, amphiphilic and hydrophilic drugs, as a function of their hydrophilic/hydrophobic properties. Bovine serum albumin (BSA) retention by hydrogels occurs in higher amounts at pH 6.9, and is influenced by electrostatic, hydrophobic forces and the swelling of the supports. Tetanus anatoxin is retained by the supports through electrostatic and/or hydrophobic forces, in amounts varying between 110 and 200mg/g. Both proteins are gradually released, through increasing of the eluent ionic strengths. Alpha-tocopherol is retained by the hydrogels preponderantly through hydrophobic forces, in amounts varying between 130 and 300mg/g. Measurement of the scavenging effect proved the antioxidant properties of the included drug. Based on the obtained results, one can appreciate the potential of the synthesized cationic hydrogels as supports for biomolecules or as vaccine adjuvants.

Direct Recognition of Superparamagnetic Nanocrystals by Macrophage Scavenger Receptor SR-AI

Scavenger receptors (SRs) are molecular pattern recognition receptors that have been shown to mediate opsonin-independent uptake of therapeutic and imaging nanoparticles, underlying the importance of SRs in nanomedicine. Unlike pathogens, engineered nanomaterials offer great flexibility in control of surface properties, allowing addressing specific questions regarding the molecular mechanisms of nanoparticle recognition. Recently, we showed that SR-type AI/II mediates opsonin-independent internalization of dextran superparamagnetic iron oxide (SPIO) nanoparticles via positively charged extracellular collagen-like domain. To understand the mechanism of opsonin-independent SPIO recognition, we tested the binding and uptake of nanoparticles with different surface coatings by SR-AI. SPIO coated with 10 kDa dextran was efficiently recognized and taken up by SR-AI transfected cells and J774 macrophages, while SPIO with 20 kDa dextran coating or cross-linked dextran hydrogel avoided the binding and uptake. Nanoparticle negative charge density and zeta-potential did not correlate with SR-AI binding/uptake efficiency. Additional experiments and computer modeling revealed that recognition of the iron oxide crystalline core by the positively charged collagen-like domain of SR-AI is sterically hindered by surface polymer coating. Importantly, the modeling revealed a strong complementarity between the surface Fe-OH groups of the magnetite crystal and the charged lysines of the collagen-like domain of SR-AI, suggesting a specific recognition of SPIO crystalline surface. These data provide an insight into the molecular recognition of nanocrystals by innate immunity receptors and the mechanisms whereby polymer coatings promote immune evasion.

Oscillatory rheometric tracing of dextran crosslinking reaction in aqueous semidilute solutions – Effects of formulation on the gelation properties

Rheological characteristics evolved during chemical gelation of semidilute dextran solutions are reported at different temperatures, levels of epichlorohydrin (ECH as a cross-linker), polymer concentration, and amount of catalyst i.e., NaOH. Increasing temperature, cross-linker, polymer and NaOH concentrations, all lead to faster gelation. Gelation at higher temperatures resulted in weaker incipient gels, whereas higher ECH addition or increasing polymer concentration gave rise to higher values of the gel strength parameter S. The results disclosed that for all systems the gelation process proceeds over a long time, and both the complex viscosity and the power law exponent reveal that solid-like gel structures are formed in the post-gel region. These results clearly show that the rheological characteristics of the incipient dextran hydrogels can be tuned by changing the conditions of temperature, polymer and cross-linker concentration, as well as the amount of catalyst.

Dextran-based hydrogel containing chitosan microparticles loaded with growth factors to be used in wound healing

Skin injuries are traumatic events, which are seldom accompanied by complete structural and functional restoration of the original tissue. Different strategies have been developed in order to make the wound healing process faster and less painful. In the present study in vitro and in vivo assays were carried out to evaluate the applicability of a dextran hydrogel loaded with chitosan microparticles containing epidermal and vascular endothelial growth factors, for the improvement of the wound healing process. The carriers' morphology was characterized by scanning electron microscopy. Their cytotoxicity profile and degradation by-products were evaluated through in vitro assays. In vivo experiments were also performed to evaluate their applicability for the treatment of skin burns. The wound healing process was monitored through macroscopic and histological analysis. The macroscopic analysis showed that the period for wound healing occurs in animals treated with microparticle loaded hydrogels containing growth factors that were considerably smaller than that of control groups. Moreover, the histological analysis revealed the absence of reactive or granulomatous inflammatory reaction in skin lesions. The results obtained both in vitro and in vivo disclosed that these systems and its degradation by-products are biocompatible, contributed to the re-establishment of skin architecture and can be used in a near future for the controlled delivery of other bioactive agents used in regenerative medicine.

Guided assembly of endothelial cells on hydrogel matrices patterned with microgrooves: a basic model for microvessel engineering

Engineering microvessel structures with spatial control has important implications for tissue engineering and regenerative medicine. We demonstrate a facile approach to integrate structural and biochemical patterns on biodegradable hydrogel matrices via combining soft-lithographic and micromolding techniques to enable self-assembly of endothelial cells toward vessel morphogenesis. Human umbilical cord vein endothelial cells (HUVECs), with or without stromal fibroblasts, were cultured on matrices made of hyaluronic acid–dextran or agarose hydrogels patterned with microgrooves containing entrapped collagen. It was found that only with appropriate microgroove geometry would the patterned matrices induce the aggregation and coalescence of endothelial cells to form microvessel-like structures. On the basis of the monoculture model, a co-culture configuration mimicking the natural vessel morphology was also established on the hyaluronic acid–dextran matrix, which contained double layered cellular assemblies through recruitment of fibroblasts to the surface of the pre-assembled endothelial cords. This study shows that the hydrogel matrices patterned with microgrooves provide a new and versatile system to enable the morphogenetic assembling of cells and warrant further studies for engineering microvessel tissues.

Functionalized, biodegradable hydrogels for control over sustained and localized siRNA delivery to incorporated and surrounding cells

Currently, the most severe limitation to applying RNA interference technology is delivery, including localizing the molecules to a specific site of interest to target a specific cell population and sustaining the presentation of these molecules for a controlled period of time. In this study, we engineered a functionalized, biodegradable system created by covalent incorporation of cationic linear polyethyleneimine (LPEI) into photocrosslinked dextran (DEX) hydrogels through a biodegradable ester linkage. The key innovation of this system is that control over the sustained release of short interference RNA (siRNA) was achieved, as LPEI could electrostatically interact with siRNA to maintain siRNA within the hydrogels and degradation of the covalent ester linkages between the LPEI and the hydrogels led to tunable release of LPEI/siRNA complexes over time. The covalent conjugation of LPEI did not affect the swelling or degradation properties of the hydrogels, and the addition of siRNA and LPEI had minimal effect on their mechanical properties. These hydrogels exhibited low cytotoxicity against human embryonic kidney 293 cells (HEK293). The release profiles could be tailored by varying DEX (8 and 12% w/w) and LPEI (0, 5, 10μg/100μl gel) concentrations with nearly 100% cumulative release achieved at day 9 (8% w/w gel) and day 17 (12% w/w gel). The released siRNA exhibited high bioactivity with cells surrounding and inside the hydrogels over an extended time period. This controllable and sustained siRNA delivery hydrogel system that permits tailored siRNA release profiles may be valuable to guide cell fate for regenerative medicine and other therapeutic applications such as cancer treatment.

Synthesis of diethylaminoethyl dextran hydrogel and its heavy metal ion adsorption characteristics

Epichlorohydrin-crosslinked diethylaminoethyl dextran (DEAE-D/ECH) hydrogel was synthesized by intermolecular side-chain reaction of DEAE-D hydroxyl groups with monomeric crosslinking agent, ECH. Swelling ability, adsorption capacity and metal removal of the hydrogel were profoundly determined and some structural parameters for the hydrogel such as volume of non-swollen gel, percentages of gellation, swelling ratio and equilibrium water content were evaluated in this study.The ability of removing heavy metal ions from Orontes River by the synthesized hydrogel, thoroughly characterized by photometric spectrometer and the adsorption characteristics of metal ions, was investigated as well as surface morphologies of the hydrogel before and after metal adsorption were examined by SEM.Structure of DEAE-D/ECH gel was analyzed by FTIR, TGA, and DSC. Gellation point of binary system reaction between DEAE-D and ECH was determined via monitoring viscosity changes during reaction. The order of affinity based on amount of metal ion uptake was found as follows: Zn2+>Mn2+>Pb2+>Cd2+.

In vivo evaluation of in situ polysaccharide based hydrogel for prevention of postoperative adhesion

In this paper, the carboxymethyl chitosan/oxidized dextran hydrogel was developed and its potency application in the prevention of postoperative adhesion was investigated. The developed hydrogel showed porous and interconnected interior structure with pore size about 250μm, which was sensitive to lysozymic solution (1.5μg/ml) with almost complete degradation after 4 weeks of in vitro incubation. In vivo study suggested that the developed hydrogel showed the great capacity on the prevention of postoperative adhesions in rat model. According to the result of histopathological examination, it clearly showed that the mesothelial cell layer of abdominal wall and cecum were completely recovered after 7 days of surgery in 3% carboxymethyl chitosan/oxidized dextran hydrogel group, while obvious adhesion between abdominal wall and cecum was observed as treatment with saline solution or 3% carboxymethyl chitosan solution after 1 day of surgery. All these results suggested that the developed biodegradable hydrogel might have potential application in the prevention of postoperative adhesion.

Injectable in situ forming glucose‐responsive dextran‐based hydrogels to deliver adipogenic factor for adipose tissue engineering

AbstractAn injectable and glucose‐responsive hydrogel derived from dextran derivatives and lectin concanavalin A (ConA) was synthesized to deliver adipogenic factor for adipose tissue engineering. The gelation is attributed to the Schiff‐base reaction cross‐linking between aldehydic and aminated dextran. To enhance adipogenesis, the adipogenic factor of insulin was incorporated in the ConA immobilized hydrogels. The gelation time, compressive modulus, morphologies, weight loss, and swelling properties of the hydrogels were investigated. The ConA triggered a competitive displacement of dextran by glucose from the lectin receptor sites, and results in increasing swelling of the gel network. The swelling ratio (SR) of ConA immobilized hydrogel showed glucose dependent properties and linearly increased from 19.8 to 31.3 at 37°C in PBS at glucose concentrations between 0 and 1.0% (w/v). The in vitro release experiments showed that the insulin would be released from this dextran hydrogel into the local microenvironment in response to glucose, thus highlighting the potential of such a injectable and biodegradable hydrogel to be used as part of implantable scaffold to delivery adipogenic factor for adipose tissue engineering. © 2012 Wiley Periodicals, Inc. J Appl Polym Sci, 2012