Unmodified Alginate Research Articles

Evaluation of dimensional stability, setting time, tensile strength, and rheological properties of kaolin clay incorporated alginate impression material

This study aims to determine and compare the dimensional stability, setting time, tensile strength, and rheological properties of kaolin clay powder-modified and unmodified alginate impression material. Commercially available alginate-based impression material was considered as a control (C) while experimental groups E-1, E-2, and E-3 were fabricated by adding 2%, 4%, and 8% of kaolin clay powder in the control, respectively. Analytical techniques were used for the characterization of the samples. A tensile strength, rheological property, dimensional stability, and setting time were recorded for control and experimental groups. FTIR analysis confirmed the presence of kaolin clay powder in all experimental groups. SEM showed a round solid structure and irregular shape particle appearance in all experimental groups as well as a control group. The dimensional stability was improved by the addition of kaolin clay powder to the alginate impression material. The percentage dimensional change at 5 min, 6, and 12 h was increased for E3 adding (8% kaolin clay powder) and decreased for the control group. The mean value of tensile strength was highest for E3 followed by E2, E1, and least in control groups. Higher Young’s Modulus and lower deformation values were measured for E3. The mean value of setting time was highest for E3 and the least was in the control group. The results for both setting time and tensile strength were very highly statistically significant (p < 0.001). The mean values of viscoelasticity, flow, and drip test were increased statistically by adding various concentrations of kaolin clay powder to the alginate impression material.

Design of mucoadhesive thiomer/organically modified montmorillonite nanocomposites: Evaluation of controlled drug release

This present work introduces a novel thiomer/nanoclay nanocomposite material with mucoadhesive and controlled release properties that has been prepared and evaluated as a potential drug carrier system. This hybrid material is based on thiolated alginate and organically modified montmorillonite (MMT). Alginate thiomer was synthesized by immobilization of l-cysteine on alginate backbone via carbodiimide reaction. Thiol/disulfide groups were identified and quantified by FT-IR, 1H NMR and Ellman's method. Rheological assays as preliminary in vitro mucoadhesion test using mucin show that complex viscosity increases until ∼7-fold compared to unmodified alginate/mucin, and G’ > G″ is present in thiomers, compared with G” > G′ present in unmodified alginate, which indicate strong interactions between thiomer and mucin. Thiomer/nanoclay nanocomposites were prepared by film casting method and characterized by TGA, XRD, TEM and rheometry. Nanocomposites maintain rheological properties showed by thiolated alginate when they are tested with mucin, increasing complex viscosity until ∼8-fold respect a nanocomposite formulation based on unmodified alginate. The release of deltamethrin from nanocomposite films was studied and the impact of the amount of nanoclay (0–7%) and four types of organic modifiers in MMT were evaluated. Different kinetic models were evaluated in order to study the mechanism involved in drug release. Zero, first, Higuchi and Korsmeyer-Peppas model were evaluated, being the last two kinetic models the ones with better fitting and higher values of R2. The presence of nanoclay on the formulation influence significantly (P < 0.001) deltamethrin short-term release showing an anomalous and Case-II transport mechanism. Compared with a Fickian diffusion when nanoclay is absent in the formulation. The diffusion coefficient D could decrease until ∼7-fold compared to a formulation without nanoclay. Long-term release is significantly influenced (P < 0.0001) by the chemical nature of organic modifier used on nanoclay and its interaction with the drug. This thiomer/nanoclay nanocomposite material could be a useful prospect as a mucoadhesive material for drug carrier with controlled drug release properties.

Tri-modified ferric alginate gel with high regenerative properties catalysts for efficient degradation of rhodamine B

Water pollution caused by dyes has become a focal point of attention. Among them, the heterogeneous Fenton reaction has emerged as an effective solution to this problem. In this study, we designed a ferric alginate gel (PAGM) tri-modified with poly(vinyl alcohol), graphene oxide, and MoS2 as a heterogeneous Fenton catalyst for organic dye degradation. PAGM addresses the drawbacks of alginate gel, such as poor mechanical properties and gel chain dissolution, thereby significantly extending the catalyst's lifespan. The removal rate of rhodamine B by PAGM reached 95.5 % within 15 min, which was 5.9 times higher than that of unmodified ferric alginate gel. Furthermore, due to the π–π interactions, PAGM exhibits unique adsorption properties for pollutants containing benzene rings. Additionally, PAGM can be regenerated multiple times through a simple soaking procedure without any performance degradation. Finally, the reaction column constructed with PAGM maintained an 83.5 % removal rate even after 319 h of continuous wastewater treatment. This work introduces a novel concept for the study of alginate-based gel catalysts in heterogeneous Fenton reactions.

Abstract P1129: Directing Revascularization In Vivo With Local Controlled Release Of An Optimized Angiogenic Growth Factor Cocktail

Reduced vascular perfusion due to aging, ischemia, or injury impedes healing and tissue function in conditions like skin ulcers and myocardial infarction, motivating development of therapies to restore vasculature locally in target tissues. We hypothesize that specific combinations of signaling molecules stimulate angiogenesis and vascular remodeling in the local tissue environment to increase perfused vessel density. Using a vascular tissue engineering approach with a fractional factorial design of experiments (DOE), we evaluated in vivo angiogenesis of combinations of ten growth factors, cytokines and/or enzymes including VEGF, bFGF, Shh, PDGF, IGF-1, EGF, TGF-β1, Ang-1, MCP-1 and MMP-9 in a subcutaneous gel plug assay in the WT immune competent rat. Our initial assessment with Matrigel identified 5 factors that maximized CD31+ vessel lumen density and aSMA+ encoated vessels at 7 days, warranting further evaluation. We developed a fully defined biomaterial system with covalently bound heparin to alginate mixed with collagen type 1 as an injectable gel. This defined biomaterial prolonged protein release up to 14 days in vitro versus Matrigel and unmodified alginate (2-4 days). The defined biomaterial was used for a second round DOE to deliver high (2 μg) and low (0.5 μg) doses of VEGF, bFGF, Shh, PDGF, and/or IGF-1. The defined biomaterial alone enhanced average lumen diameter 15-fold and endothelial cell infiltration 12-fold versus Matrigel. Perfused lumen density increased 16-fold with high Shh; aSMA-positive lumen wall area increased 4-fold with high VEGF, PDGF, and IGF-1; perfused vessel size increased 3-fold with high VEGF, bFGF, and Shh; and endothelial cell recruitment increased 2-fold with high IGF-1 relative to unloaded controls after 7 days in vivo. Empirical testing of 2- to 5-factor combinations showed that cocktail potency required initiation of angiogenic sprouting by VEGF or bFGF and vascularization responses were strongest in the presence of Shh and IGF-1. In conclusion, we identified sets of highly potent cocktails and leveraged controlled release from a defined biomaterial as a tailored revascularization therapy for local angiogenesis, vascular remodeling, and tissue regeneration.

Biopolymer sodium alginate based titania and magnetite nanocomposites as natural corrosion inhibitors for mild steel in acidic medium

Green biopolymeric materials and its hybrid nanocomposites, i.e. sodium alginate grafted polymethylmethacrylate based titanium dioxide and iron oxide (SA-g-PMMA/TiO2 and SA-g-PMMA/Fe3O4) have been explored for the prevention of mild steel's corrosion in 15% HCl. It is reflected from the electrochemical impedance data that SA-g-PMMA/TiO2 exhibits maximum inhibition efficiency of 97.28% followed by SA-g-PMMA/Fe3O4 that gives 96.82% efficiency while the unmodified sodium alginate possess merely 84.74% efficiency. The declining trend of inhibition efficiency with rising temperature has been explained through gravimetric studies conducted at 303 K- 333 K. The thermodynamic activation and adsorption parameters revealed the mixed mode of adsorption of inhibitors over mild steel surface which follow Langmuir adsorption isotherm. It has been observed from tafel polarization studies that all studied inhibitors are mixed type in nature. The surface morphological inspection of the mild steel samples was done through FE-SEM and AFM, which revealed the formation of better protective adsorption layer over the exposed metallic surface by the nanocomposites in comparison to sodium alginate alone. In addition to this, the elemental composition of adsorbed film on inhibited mild steel specimens was obtained by XPS technique. Quantum parameters obtained through Density Functional Theory (DFT) further corroborate the experimental outcomes.

Secreted metabolome of porcine blastocysts encapsulated within in vitro 3D alginate hydrogel culture systems undergoing morphological changes provides insights into specific mechanisms involved in the initiation of porcine conceptus elongation.

The exact mechanisms regulating the initiation of porcine conceptus elongation are not known due to the complexity of the uterine environment. To identify contributing factors for initiation of conceptus elongation in vitro , this study evaluated differential metabolite abundance within media following culture of blastocysts within unmodified alginate (ALG) or Arg-Gly-Asp (RGD)-modified alginate hydrogel culture systems. Blastocysts were harvested from pregnant gilts, encapsulated within ALG or RGD or as non-encapsulated control blastocysts (CONT), and cultured. At the termination of 96h culture, media were separated into blastocyst media groups: non-encapsulated control blastocysts (CONT); ALG and RGD blastocysts with no morphological change (ALG- and RGD-); ALG and RGD blastocysts with morphological changes (ALG+ and RGD+) and evaluated for non-targeted metabolomic profiling by liquid chromatography (LC)-mass spectrometry (MS) techniques and gas chromatography-(GC-MS). Analysis of variance identified 280 (LC-MS) and 1 (GC-MS) compounds that differed (P <0.05), of which 134 (LC-MS) and 1 (GC-MS) were annotated. Metabolites abundance between ALG+ vs ALG-, RGD+ vs RGD-, and RGD+ vs ALG+ were further investigated to identify potential differences in metabolic processes during the initiation of elongation. This study identified changes in phospholipid, glycosphingolipid, lipid signalling, and amino acid metabolic processes as potential RGD-independent mechanisms of elongation and identified changes in lysophosphatidylcholine and sphingolipid secretions during RGD-mediated elongation. These results illustrate changes in phospholipid and sphingolipid metabolic processes and secretions may act as mediators of the RGD-integrin adhesion that promotes porcine conceptus elongation.

Fabrication and structural characterisation of self-crosslinking hydrogel based on Vietnamese sources of chitosan and alginate

Hydrogel materials have attracted extensive research over the last few decades, especially in tissue engineering, due its many comparable properties with native tissue. This study proposes a new approach to hydrogel fabrication that combines oxidized alginate (OA) into N,O-carboxymethyl chitosan (NOCC) and an oxidized hyaluronan-based hydrogel system employing low cost, domestically sourced chitosan and alginate. Hydrogel fabrication parameters including component ratio and hydrogel concentration were studied. Fourier transform infrared spectroscopy (FT-IR) analysis was applied to confirm the chemical structure of the modified materials. Fabricated hydrogel samples were assessed by cross-sectional surface morphology, equilibrium swelling degree, and in vitro degradation behaviour. The results revealed NOCC and oxidized hyaluronic acid (OHA)-OA component contributions toward hydrogel properties, a threshold of raising total polymer content within the network, and a comparison with previous formulations using unmodified alginate. Using low cost domestic resources is a promising way to reduce fabrication expenses, and further work should be performed to evaluate the potential of this cost-effective hydrogel for the tissue engineering field.

Bioactive and degradable hydrogel based on human platelet-rich plasma fibrin matrix combined with oxidized alginate in a diabetic mice wound healing model

In the present study we developed an injectable, bioactive and degradable hydrogel composed of alginate at 2.5% oxidation degree and calcium-activated platelet rich plasma (PRP) for wound healing applications (PRP-HG-2.5%). The alginate gives mechanical support to the hydrogel while the activated PRP provides growth factors that enhance wound healing and fibrin which creates an adequate microenvironment for cell migration and proliferation. The rheological and mechanical properties of the hydrogel were characterized. Further characterization revealed that PRP-HG-2.5% showed a faster hydrolitic degradation rate than unmodified alginate and a similar platelet derived growth factor (PDGF-BB) release profile. In vitro efficacy studies, carried out in human fibroblasts and keratinocytes, showed that PRP-HG-2.5% was not cytotoxic and that it was able to promote cell adhesion and proliferation. Thereafter, in an in vivo full thickness wound healing study conducted in diabetic mice, no differences were found among PRP-HG-2.5% and its counterpart without PRP, likely due to the xenogeneic origin of the PRP. This hypothesis was validated in vitro, since a cytotoxic effect was observed after human PRP application to mouse fibroblasts. Therefore, PRP-HG-2.5% might be a promising strategy for chronic woundstreatment, although its effectiveness should be evaluated in a more reliable preclinical model.

Modification of sodium alginate by octenyl succinic anhydride to fabricate beads for encapsulating jujube extract

The effect of modification of sodium alginate on the beads properties was investigated and compared with unmodified alginate beads. The effect of storage conditions on the shelf life of the beads was determined. The modification of sodium alginate was achieved with octenyl succinic anhydride (OSA). Antioxidant activity and total phenolic compounds of the jujube extract was evaluated. Some physical and structural properties yield and encapsulation efficiency of the beads were measured. The encapsulation yield of the beads was significantly affected by modification of sodium alginate. The highest yield was observed in the alginate stored at ambient temperature on the day 14th which was 35.21%. The average beads size of alginate was 5.10 and 4.68 mm in modified and unmodified alginate beads, respectively. Modification also had a significant effect on the hardness of the beads. Higher Tg which ensures good product stability in thermal process was clearly seen in the modified beads maintained at ambient temperature. Fourier Transform Infrared Spectroscopy (FT-IR) revealed the existence of OH groups in the extract-loaded beads. These findings have important implications on designing preservation and delivery systems of soluble bioactive compounds of jujube extract to apply in development of new functional foods and drinks.

Engineering alginate microparticles for optimized accumulation in fetal rat myelomeningocele

IntroductionIntraamniotic microparticle injection is a novel technique for the treatment of myelomeningocele (MMC) in which microparticles are delivered in-utero in a minimally invasive fashion to bind to and protect the exposed spinal cord. This technique could offer earlier intervention and greater access to prenatal treatment of MMC. Here we demonstrate progress on the engineering of the microparticles to promote binding to the MMC defect. We hypothesized that when the particle's surface charge was decreased and delivery concentration increased, particles would bind to the MMC defect more frequently and more specifically. MethodsAlginate microparticles underwent surface modification to alter the particle charge. Dye-loaded alginate, alginate- dextran sulfate, and alginate- chitosan were injected on e17 into the amnion of a rat model of MMC and the incidence of successful binding and specificity of particle binding to the MMC defect were calculated. Specificity of binding was described using a defect-to-skin brightness ratio based on specimen imaging. Comparisons were made with chi-square, p< 0.05 marked significance. ResultsThere was no difference in the incidence of successful binding at e17 with 0.6 mg/fetal kg between the three tested alginate particles. However, alginate- dextran sulfate bound most specifically to the defect (p< 0.05). Alginate-dextran sulfate also demonstrated more frequent binding at higher doses than lower doses (79% at 1.2 mg/kg vs 38% at 0.6 mg/kg and 24% at 0.8 mg/kg, p< 0.01 for both). Specificity was not sacrificed at higher dose injections: defect-to-skin brightness ratio of 5.4 at 1.2 mg/kg vs 1.8 at 0.6 mg/kg (p< 0.05) ConclusionWe demonstrate that the intraamniotic injection of alginate-dextran sulfate microparticles at high concentration bind more frequently and more specifically to MMC defects than the previously tested unmodified alginate microparticles.

Influences of Molecular Weights on Physicochemical and Biological Properties of Collagen-Alginate Scaffolds.

For tissue engineering applications, biodegradable scaffolds containing high molecular weights (MW) of collagen and sodium alginate have been developed and characterized. However, the properties of low MW collagen-based scaffolds have not been studied in previous research. This work examined the distinctive properties of low MW collagen-based scaffolds with alginate unmodified and modified by subcritical water. Besides, we developed a facile method to cross-link water-soluble scaffolds using glutaraldehyde in an aqueous ethanol solution. The prepared cross-linked scaffolds showed good structural properties with high porosity (~93%) and high cross-linking degree (50–60%). Compared with collagen (6000 Da)-based scaffolds, collagen (25,000 Da)-based scaffolds exhibited higher stability against collagenase degradation and lower weight loss in phosphate buffer pH 7.4. Collagen (25,000 Da)-based scaffolds with modified alginate tended to improve antioxidant capacity compared with scaffolds containing unmodified alginate. Interestingly, in vitro coagulant activity assay demonstrated that collagen (25,000 Da)-based scaffolds with modified alginate (C25-A63 and C25-A21) significantly reduced the clotting time of human plasma compared with scaffolds consisting of unmodified alginate. Although some further investigations need to be done, collagen (25,000 Da)-based scaffolds with modified alginate should be considered as a potential candidate for tissue engineering applications.

Design and Investigation of Penetrating Mechanism of Octaarginine-Modified Alginate Nanoparticles for Improving Intestinal Insulin Delivery

The aim of the study is to design octaarginine (R8)-modified insulin-alginate nanoparticles (INS-SA/R8 NPs) as the oral insulin delivery system, and further investigate its penetrating mechanism. The characterization results indicated that the surface of INS-SA/R8 NPs was smooth and the average diameter was about 300 nm. INS-SA/R8 NPs exhibited a stronger stability in the simulated gastrointestinal fluids and had a better controlled release than unmodified alginate nanoparticles (INS-SA NPs). Moreover, INS-SA/R8 NPs group had the strongest insulin transport capacity and the largest amount of insulin uptake in all experimental groups. Most importantly, the improvement of insulin intestinal uptake was further confirmed in rat intestine in vivo, and its penetrating mechanism might be involved in the production of endogenous nitric oxide (NO) signal molecule. In addition, in vivo hypoglycemic studies showed that orally administrated INS-SA/R8 NPs produced a better hypoglycemic effect as compared with INS-SA NPs in diabetic rats. Meanwhile, from the cytotoxicity analysis, INS-SA/R8 NPs were safe for oral administration. Taken together, INS-SA/R8 NPs was a good oral insulin delivery system, which might also be suitable for other protein drugs.

Urea formaldehyde modified alginate beads with improved stability and enhanced removal of Pb2+, Cd2+, and Cu2+

Urea formaldehyde (UF) was grafted onto the backbone of alginate to prepare microbeads as an adsorbent for the removal of heavy metal ions from aqueous solutions. The expensive alginate was crosslinked with cheaper UF at different ratios (1: 2.5∼1: 12.5) to produce sturdy alginate-UF beads at lower cost. Characterization results showed that UF modification enhanced the pore network and structural stability of the beads, which can be attributed to the reduced intermolecular forces and plentiful of nitrogen and oxygen donor atoms of the beads. The swelling of air-dried alginate-UF beads in different solutions was much lower than that of the unmodified alginate beads, confirming the improved stability. The replacement of alginate with UF at different ratios either did not affect or increased the adsorption of heavy metal ions (Pb2+, Cd2+, and Cu2+) on the beads. For example, the adsorption capacities of Pb2+, Cd2+, and Cu2+ on air-dried alginate-UF (1: 2.5) beads were 1.66, 0.61, and 0.80 mmol/g, which were 39.88%, 9.29%, and 9.52% higher than those of the corresponding unmodified alginate beads, respectively. The adsorption of heavy metals on the alginate-UF beads was mainly controlled by ion exchange, complexation, and electrostatic interaction mechanisms.

Preparation and flocculation performance study of a novel amphoteric alginate flocculant

Sodium alginate is a natural biomacromolecule with promising applications as a flocculant for wastewater treatment due to its biodegradability and non-toxicity. To enhance the flocculating efficiency, simplify the synthetic process of the flocculants and expand the application scope of alginate, a novel amphoteric flocculant was synthesized through reaction of alginate with 3-chloro-2-hydroxypropyltrimethyl ammonium chloride under alkaline conditions. The structures of the flocculants were characterized using various methods. The flocculants demonstrated nanoparticle sizes with a narrow distribution. The amphoteric flocculant could not only effectively remove the positively-charged Pb2+ from wastewater, but also removed the negatively-charged humic acid. Under optimum conditions, the removal rates reached 92.32% and 95.18% for Pb2+ and humic acid, respectively. Compared with unmodified alginate, the amphoteric flocculant had significantly improved flocculation for the heavy metal ions and negatively-charged pollutants. The flocculating mechanism for heavy metals was chelating, and was confirmed by X-ray photoelectron spectroscopy, and the flocculating mechanism for humic acid was electric neutralization. The adsorption isotherm could be described by a Langmuir model. The flocculation process accorded with quasi-second-order kinetics equation. This novel amphoteric flocculant has promising applications as an environmentally-friendly treatment agent for wastewater.

Self-crosslinked hydrogel with delivery carrier obtained by incorporation of oxidized alginate microspheres into gelatin matrix

A novel self-crosslinked hydrogel with a delivery carrier was prepared by incorporating 0.5, 1, and 4% (w/v) oxidized alginate di-aldehyde microspheres (Ads) into a 5% (w/v) gelatin matrix. The Ads have a two-fold function. Namely, they act as delivery vehicles and promote the self-crosslinking of the hybrid hydrogel. Both light and scanning electron microscopy confirmed a homogenous distribution of the Ads in the gelatin matrix. In contrast to the unmodified alginate microspheres, clustering and sedimentation could be avoided. Furthermore, their incorporation improved the mechanical properties and the thermal stability of the thermosensitive gelatin. Crosslinking was completed after 213 min at 37 °C. The addition of 1% (w/w) borax shortened the crosslinking process to 59.5 min. The crosslinking time could be further reduced to 20 min by performing the Schiff base reaction at an elevated temperature of 45 °C.

Preparation and physicochemical properties of an injectable alginate-based hydrogel by the regulated release of divalent ions via the hydrolysis of d-glucono-δ-lactone.

In this study, an injectable dopamine-modified alginate hydrogel combined with nano-hydroxyapatite or strontium hydroxyapatite was cross-linked via the in situ slow release of divalent ions from the hydrolysis of D-glucono-δ-lactone (GDL). The cross-linking mechanism involved the chelation of an alginate with divalent ions and the hydrogen-bonding interaction between alginate and catechol groups. As the GDL concentration at 0.5% (w/v) regulated the release of the divalent ions, which enhanced the chelation effect, it was investigated, and inorganic nanoparticles were homogeneously distributed into the hydrogel system to improve the mechanical properties and stabilize the hydrogel network. Furthermore, the effects of dopamine on the improvement of the mechanical properties were investigated. Results demonstrated that the compressive strength of this injectable hydrogel is enhanced by 4.6 times compared with that of the hydrogel without the addition of GDL, and the compressive strength is enhanced by 4.0 times compared with that of the unmodified alginate hydrogel at strain values ranging from 10% to 50%. The hydrogels combined with strontium hydroxyapatite exhibited a more compact, suitable pore size, with a three-dimensional network structure, and the particle size was 50–100 μm; this range of values is considered as optimal for the growth of bone tissues. In addition, the gelation time can be adjusted from a few minutes to a few seconds by adjusting experiment variables. Our study provides a potential method for improving the mechanical properties of bone tissue engineering materials. 1HNMR, FTIR, and UV–vis spectroscopy measurements; XRD and SEM; and pH, ion release, and mechanical tests were carried out.

Preparation of Liver-targeted Nano-prodrug Based on Sodium Alginate Derivative and the Study on Antitumor Activity†

The high viscosity of sodium alginate( ALG) causes its insufficient targeted ligand loading,and further influences the targeted recognition effect of nano-prodrug. Here,oligomeric ethylene glycol modified-sodium alginate( ALG-mOEG) was used as a carrier to improve the targeted-ligands loading. Results showed that ALG-mOEG significantly improved glycyrrhetinic acid( GA) loading compared with unmodified ALG( 11. 8%vs. 6. 9%,1. 97-fold increase). On this basis,the liver targeted nano-prodrug( DOX-ALG-mOEG /GA-ALGmOEG NPs) was self-assembled via dialysis method by mixing GA-ALG-mOEG and DOX-ALG-mOEG. Cell cytotoxicity experiment showed that DOX-ALG-mOEG /GA-ALG-mOEG NPs inhibited HepG2 proliferation with an half maximal inhibitory concentration( IC50) value of 58.1 ng/mL while the IC50 of control group was141. 7 ng /mL; the tumor growth inhibition rate( IR) reached to 88. 4%,improved by 11. 5% compared to that of the control group. This study show that the liver targeted nano-prodrug based on ALG-mOEG can effectively improve the drug utilization,and provide a reference for the preparation of other polysaccharide targeted nanoprodrug.

Surface molecularly imprinted amino-functionalized alginate microspheres for enantio-selective extraction of l-ascorbic acid

A surface molecular imprinting technique was utilized in the fabrication of an enantio-selective adsorbent based on amino-functionalized alginate microspheres for chiral resolution of ascorbic acid. Alginate microspheres were first strengthened via epichlorohydrin (ECH) covalent cross-linking then functionalized with amino groups through graft copolymerization of polyacrylamide (PAm) followed by Hofmann degradation. Surface molecular imprinting was then performed under mild conditions by ionic interaction between the surface incorporated amine groups and the template l-ascorbic acid enantiomers followed by cross-linking with glyoxal. l-Ascorbic acid enantio-selective adsorbent (LA-Alg) was finally obtained by removing the template molecules out of the cross-linked network formed on the surface of the modified alginate particles. The synthetic steps were monitored using elemental analysis and FTIR spectra. Also, the surface morphologies of the native unmodified alginate along with both imprinted and non-imprinted adsorbent particles were examined by SEM. Moreover, the crystalline profile and thermal properties of both native and modified samples were investigated using XRD spectra and thermogravimetric analysis (TGA), respectively. The effect of pH on the extraction process was studied and indicated that the maximum adsorption was obtained at pH 4. Also, adsorption isotherms over LA-Alg adsorbent displayed the best fit with Langmuir model with maximum adsorption capacity 116 ± 1 and 67 ± 1 mg/g with respect to both l- and d-ascorbic acid, respectively. Moreover, the chiral resolution experiment using batch technique indicated 72% enantiomeric excess.

In Vitro and In Vivo Biocompatibility Evaluation of Polyallylamine and Macromolecular Heparin Conjugates Modified Alginate Microbeads

Host reactivity to biocompatible immunoisolation devices is a major challenge for cellular therapies, and a human screening model would be of great value. We designed new types of surface modified barium alginate microspheres, and evaluated their inflammatory properties using human whole blood, and the intraperitoneal response after three weeks in Wistar rats. Microspheres were modified using proprietary polyallylamine (PAV) and coupled with macromolecular heparin conjugates (Corline Heparin Conjugate, CHC). The PAV-CHC strategy resulted in uniform and stable coatings with increased anti-clot activity and low cytotoxicity. In human whole blood, PAV coating at high dose (100 µg/ml) induced elevated complement, leukocyte CD11b and inflammatory mediators, and in Wistar rats increased fibrotic overgrowth. Coating of high dose PAV with CHC significantly reduced these responses. Low dose PAV (10 µg/ml) ± CHC and unmodified alginate microbeads showed low responses. That the human whole blood inflammatory reactions paralleled the host response shows a link between inflammatory potential and initial fibrotic response. CHC possessed anti-inflammatory activity, but failed to improve overall biocompatibility. We conclude that the human whole blood assay is an efficient first-phase screening model for inflammation, and a guiding tool in development of new generation microspheres for cell encapsulation therapy.

Paradigm Shift for Preparing Versatile M2+-Free Gels from Unmodified Sodium Alginate.

This manuscript describes a new route to prepare rapidly Ca2+-free hydrogels from unmodified sodium alginate by simply mixing with small organic molecules such as poly(carboxylic acid) compounds as cross-linker agents instead of classical divalent metal salts such as CaCl2. Dimethyl sulfoxide (DMSO) was also found to induce the rapid gelation of aqueous alginate solutions. The gelation process takes place at room temperature, and depending on the composition, gels with good thermal (90-100 °C) and mechanical properties compared to classical metal-containing analogs are obtained. DMSO-based gels showed remarkable self-supporting and thixotropic properties, which can be tuned by the biopolymer concentration. Furthermore, oxalic acid-based gels show superior elasticity than HCl, CaCl2 and DMSO-based gels. The possibility to prepare monoliths, beads, and films of these gels provide them with significant versatility. In particular, films made of alginate and oxalic acid show good potential as synergistic anticancer drug delivery carrier. Computational studies using both quantum mechanical and classical force-field methodologies reveal that hydrogen bonding networks between water and DMSO molecules located close to the alginate chains are responsible for the stability of DMSO-based gels. In contrast, the cohesion of oxalic acid-based gels is a consequence of the coexistence of multiple ionic associations involving oxalate, alginate, and Na+ counterions, which stabilize the system and keep all the interacting species grouped.