Crosslinking Solution Research Articles

Impact of Glutaraldehyde on In Vivo Colon-Specific Release of Resveratrol from Biodegradable Pectin-Based Formulation

Despite potential therapeutic efficacy of resveratrol on colitis and colorectal cancer, rapid absorption and metabolism at the upper gastro-intestinal (GI) tract prevent its clinical application. To overcome this, we attempted to develop colon-specific multi-particulate calcium-pectinate (Ca-pectinate) formulations of resveratrol. However, they were unable to prevent premature drug release at the upper GI tract. Thus, glutaraldehyde (Glu) was used for further cross-linking of the pectin chains. The formulation conditions and procedure were optimized from the in vitro drug release study. The optimized formulation was subjected to in vivo pharmacokinetic study in rats and compared with the unmodified Ca-pectinate and suspension formulation of resveratrol. Spherical particles (∼1 mm diameter) with high drug encapsulation were produced. Low cross-linking solution pH (1.5), minimum Glu concentration (2.5%) and cross-linking time (2 h) were crucial to exhibit colon-specific drug release. As Glu was added in the cross-linking solution, cross-linking between pectin chains and Glu occurred simultaneously during Ca-pectinate network formation, which appeared as a cost-effective formulation technique. Most importantly, the pharmacokinetic study demonstrated in vivo colon-specific drug release from the optimized formulation, while faster drug release was observed from the unmodified and suspension formulations. Hence, the developed formulation has potential to be used as colon-specific delivery system of resveratrol.

Design and development of gliclazide-loaded chitosan for oral sustained drug delivery: In vitro/in vivo evaluation

Gliclazide (GLZ)/Chitosan microparticles were prepared with tripolyphosphate (TPP) by ionic cross-linking. The particle sizes of TPP–chitosan microparticles were in the range 675–887 µm and the loading efficiencies of drug was more than 94.0%. Chitosan concentration, TPP solution pH and glutaraldehyde volume added to the TPP cross-linking solution had an effect on the drug release characteristics. The microparticles were examined with scanning electron microscopy and infrared spectroscopy. Furthermore, pectin can interact with cationic chitosan on the surface of these TPP/chitosan microparticles to form a polyelectrolyte complex film for the improvement of the drug sustained-release performances. In vivo testing of the GLZ–chitosan microparticles in diabetic albino rabbits demonstrated significant antidiabetic effect of GLZ/chitosan microparticles after 8 h which lasts for 18 h, compared with GLZ powder which produced maximum hypoglycaemic effect after 4 h, suggesting that GLZ/chitosan microparticles are a valuable system for the long-term delivery of GLZ.

Flexible Low-Voltage Organic Thin-Film Transistors Enabled by Low-Temperature, Ambient Solution-Processable Inorganic/Organic Hybrid Gate Dielectrics

We report here on the design, synthesis, processing, and dielectric properties of novel cross-linked inorganic/organic hybrid blend (CHB) dielectric films which enable low-voltage organic thin-film transistor (OTFT) operation. CHB thin films (20-43 nm thick) are readily fabricated by spin-coating a zirconium chloride precursor plus an α,ω-disilylalkane cross-linker solution in ambient conditions, followed by curing at low temperatures (~150 °C). The very smooth CHB dielectrics exhibit excellent insulating properties (leakage current densities ~10(-7) A/cm(2)), tunable capacitance (95-365 nF/cm(2)), and high dielectric constants (5.0-10.2). OTFTs fabricated with pentacene as the organic semiconductor function well at low voltages (<-4.0 V). The morphologies and microstructures of representative semiconductor films grown on CHB dielectrics prepared with incrementally varied compositions and processing conditions are investigated and shown to correlate closely with the OTFT response.

Diffusion loading and drug delivery characteristics of alginate gel microparticles produced by a novel impinging aerosols method

Microencapsulation of a hydrophilic active (gentamicin sulphate (GS)) and a hydrophobic non-steroidal anti-inflammatory drug (ibuprofen) in alginate gel microparticles was accomplished by molecular diffusion of the drug species into microparticles produced by impinging aerosols of alginate solution and CaCl2 cross-linking solution. A mean particle size in the range of 30–50 µm was measured using laser light scattering and high drug loadings of around 35 and 29% weight/dry microparticle weight were obtained for GS and ibuprofen respectively. GS release was similar in simulated intestinal fluid (phosphate buffer saline (PBS), pH 7.4, 37°C) and simulated gastric fluid (SGF) (HCl, pH 1.2, 37°C) but was accelerated in PBS following incubation of microparticles in HCl. Ibuprofen release was restricted in SGF but occurred freely on transfer of microparticles into PBS with almost 100% efficiency. GS released in PBS over 7 h, following incubation of microparticles in HCl for 2 h was found to retain at least 80% activity against Staphylococcus epidermidis while Ibuprofen retained around 50% activity against Candida albicans. The impinging aerosols technique shows potential for producing alginate gel microparticles of utility for protection and controlled delivery of a range of therapeutic molecules.

In-line formation of chemically cross-linked P84 ® co-polyimide hollow fibre membranes for H 2/CO 2 separation

In this study, chemically cross-linked asymmetric P84 ® co-polyimide hollow fibre membranes with enhanced separation performance were fabricated, using a dry-wet spinning process with an innovative in-line cross-linking step. The chemical modification was conducted by controlled immersion of the coagulated fibre in an aqueous 1,5-diamino-2-methylpentane (DAMP) cross-linker solution before the take-up. The effect of the cross-linker concentration on the thermal, mechanical, chemical and gas transport properties of the membranes was investigated. FT-IR/ATR analysis was used to identify the chemical changes in the polymer, while DSC analysis confirmed the changes in the T g and the specific heat of the polymer upon cross-linking. Chemical cross-linking with a 10 wt.% aqueous DAMP solution strongly enhanced the H 2/CO 2 ideal selectivity from 5.3 to 16.1, while the H 2 permeance of the membranes decreased from 7.06 × 10 −3 to 1.01 × 10 −3 m 3 (STP) m −2 h −1 bar −1 for a feed pressure of 1 bar at 25 °C. The increase of selectivity with decreasing permeance is somewhat higher than the slope in the Robeson upper bound, evidencing the positive effect of the cross-linking on the separation performance of the fibres. Simultaneously, the cross-linking leads to improved mechanical resistance of the membranes, which could be further enhanced by an additional thermal treatment. The produced membranes are therefore more suitable for use under harsh conditions and have a better overall performance than the uncross-linked ones.

Influence of crosslinkers and crosslinking method on the properties of gelatin films extracted from leather solid waste

AbstractGelatin was extracted from chrome tanned leather waste with the aim to produce a durable coating or film. Crosslinking has shown to improve the physical performance of a film/coating. The effect of the method of crosslinking and the use of different crosslinking agents were studied. The extracted gelatin was crosslinked either by immersion of preformed films into a crosslinker solution (Method A) or by the addition of the crosslinking reagent to the gelatin solution prior to film formation (Method B). The different results obtained between both methods may be due to: the relative concentration of crosslinking reagent, the introduction of crosslinks within different regions of gelatin (triple helical regions and random coil regions), and the reaction rate. Method A of crosslinking is more likely to form crosslinks outside but close to the triple helical regions, disrupting the order and stability of the helical structure. Crosslinks may form preferentially within the random coil regions when Method B of crosslinking is used. Both methods led to the formation of chemical crosslinks in the extracted gelatin films, as demonstrated by the reduction of the degree of aqueous swelling and the proportion of low molecular weight fractions. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

The influence of butyl acrylate/methyl methacrylate/2-hydroxy ethyl methacrylate/acrylic acid latex properties on pressure sensitive adhesive performance

Pressure sensitive adhesives (PSAs) were produced using latexes synthesized via a starved seeded semi-batch emulsion polymerization process with butyl acrylate (BA), methyl methacrylate (MMA) and sometimes additional monomers, 2-hydroxy ethyl methacrylate (HEMA) and/or acrylic acid (AA). For the BA/MMA comonomer latexes, the amount of cross-linker (allyl methacrylate), monomer emulsion and initiator solution feeding times, and the BA/MMA weight ratio were manipulated to vary the polymer properties. The performance of PSA films cast from these latexes was evaluated by tack, peel strength and shear strength. The effect of polymer properties on PSA performance was related to the viscoelastic properties of the PSAs. For BA/MMA latexes, it was not possible to greatly improve the peel strength even at great sacrifice of shear strength for PSAs with gel contents of ∼60 wt% or higher. This was because the ratio of the loss modulus at debonding frequency to the storage modulus at bonding frequency did not vary significantly for the conditions studied. The addition of HEMA provided a significant influence on latex polymer properties as well as PSA performance for both high (>60 wt%) and low (∼20 wt%) gel contents. For some cases, tack, peel strength and shear strength were simultaneously and greatly improved by the addition of HEMA. Adding both AA and HEMA while decreasing the amount of emulsifier, also resulted in a PSA with much better performance (i.e., higher tack, peel strength and shear strength) than a BA/MMA PSA with similar gel content (∼60 wt%).

The Effect of Oxygen on Viscosity of the Cross-Linking Polymer

Recently, to prohibit water cut from rising, reduce the low efficient or inefficient recycle of the injection fluid in the high permeability of the reservoir and enhance the economic benefits of the exploitation, oilfield in the east of domestic has done a series of research studies on the nature of profile modification agent and the effect of pilot test. A good effect was obtained, but there still exist some factors influencing the properties of the profile modification solution. It means that the viscosity of Cr3+, Al3+, and compound ion cross-linked polymer solution in the anaerobic and aerobic environment were studied. After the solutions were added to the bactericide, the retention effect of viscosities and the gel were studied in an anaerobic and an aerobic environment. The results showed that the viscosity of the cross-linked polymer solution prepared by the produced water in an aerobic environment was higher than that of the cross-linked polymer solution prepared by produced water in an anaerobic environment. To some extent, the viscosity of the cross-linked polymer solutions added to bactericide was improved. The cross-linked polymer solution has a good gel action in anaerobic environment.

Role of Direct Interactions between the Histone H4 Tail and the H2A Core in Long Range Nucleosome Contacts

In eukaryotic nuclei the majority of genomic DNA is believed to exist in higher order chromatin structures. Nonetheless, the nature of direct, long range nucleosome interactions that contribute to these structures is poorly understood. To determine whether these interactions are directly mediated by contacts between the histone H4 amino-terminal tail and the acidic patch of the H2A/H2B interface, as previously demonstrated for short range nucleosomal interactions, we have characterized the extent and effect of disulfide cross-linking between residues in histones contained in different strands of nucleosomal arrays. We show that in 208-12 5 S rDNA and 601-177-12 nucleosomal array systems, direct interactions between histones H4-V21C and H2A-E64C can be captured. This interaction depends on the extent of initial cross-strand association but does not require these specific residues, because interactions with residues flanking H4-V21C can also be captured. Additionally, we find that trapping H2A-H4 intra-array interactions antagonizes the ability of these arrays to undergo intermolecular self-association.

Biodegradation of Methyl Tert-butyl Ether in a Bioreactor using Immobilized Methylibium petroleiphilum PM1 Cells

Methylibium petroleiphilum PM1, which is capable of degrading of methyl tert-butyl ether (MTBE), was immobilized in calcium alginate gel beads. Various applications were explored to increase the mechanical strength of these gel beads. The introduction of 0.3 mol/L calcium chloride into the crosslinking solution, 0.002 mol/L calcium chloride into the growth medium, and 0.2% polyethyleneimine (PEI) as chemical crosslinking agent increased the stability of the Ca-alginate gel beads under the operation conditions of the bioreactor. The degradation rates of MTBE by the immobilized cells in the bioreactor system operated in batch and continuous mode , respectively, were compared. A MTBE biodegradation rate of 5.79 mg/L·h was reached for over 400 h (50 batches), and the immobilized cells in the bioreactor removed >96% MTBE during 50 days of operation. Molecular analysis of the PM1 cells revealed that microbial growth occurred predominantly as microcolonies in the outer area of the beads during the first 20 days of operation. The results of this study show that a continuous-mode, fixed-bed bioreactor reactor coupled with PM1-immobilized cells is a promising technology for remediating MTBE-contaminated groundwater.

Regulating in vivo calcification of alginate microbeads

Alginate calcification has been previously reported clinically and during animal implantation; however no study has investigated the mechanism, extensively characterized the mineral, or evaluated multiple methods to regulate or eliminate mineralization. In the present study, alginate calcification was first studied in vitro: calcium-crosslinked alginate beads sequestered surrounding phosphate while forming traces of hydroxyapatite. Calcification in vivo was then examined in nude mice using alginate microbeads with and without adipose stem cells (ASCs). Variables included the delivery method, site of delivery, sex of the animal, time in vivo, crosslinking solution, and method of storage prior to delivery. Calcium-crosslinked alginate microbeads mineralized when injected subcutaneously or implanted intramuscularly after 1–6 months. More extensive analysis with histology, microCT, FTIR, XRD, and EDS showed calcium phosphate deposits throughout the microbeads with surface mineralization that closely matched hydroxyapatite found in bone. Incorporating 25 mm bisphosphonate reduced alginate calcification whereas using barium chloride eliminated mineralization. Buffering the crosslinking solution with HEPES at pH 7.3 while washing and storing samples in basal media prior to implantation also eliminated calcification in vivo. This study shows that alginate processing prior to implantation can significantly influence bulk hydroxyapatite formation and presents a method to regulate alginate calcification.

A Fused α-β “Mini-spectrin” Mimics the Intact Erythrocyte Spectrin Head-to-head Tetramer

Head-to-head assembly of two spectrin heterodimers to form an actin-cross-linking tetramer is a physiologically dynamic interaction that contributes to red cell membrane integrity. Recombinant beta-spectrin C-terminal and alpha-spectrin N-terminal peptides can form tetramer-like univalent complexes, but they cannot evaluate effects of the open-closed dimer interactions or lateral associations of the two-spectrin strands on tetramer formation. In this study we produced and characterized a fused "mini-spectrin dimer" containing the beta-spectrin C-terminal region linked to the alpha-spectrin N-terminal region. This fused mini-spectrin mimics structural and functional properties of intact, full-length dimers and tetramers, including lateral association of the alpha and beta subunits in the dimer and formation of a closed dimer. High performance liquid chromatography gel filtration analyses of this mini-spectrin provide the first direct non-imaging experimental evidence for open and closed spectrin dimers and show that dimer-tetramer-oligomer interconversion is slow at low temperatures and accelerated at 30 degrees C, analogous to full-length spectrin. This protein exhibits wild type dimer-tetramer dissociation constants of approximately 1 mum at 30 degrees C, independent of initial oligomeric state. Conformational states of the mini-spectrin dimer were probed further using chemical cross-linking, which identified distinct groups of cross-links for "open" and "closed" dimers and confirmed the N-terminal region of alpha-spectrin remains highly flexible in the complex, exhibiting closely analogous structures to those observed for the isolated alpha-spectrin N-terminal using NMR (Park, S., Caffrey, M. S., Johnson, M. E., and Fung, L. W. (2003) J. Biol. Chem. 278, 21837-21844). This fusion protein should serve as a useful template for structural and functional studies of the divalent tetramer site.

Development of hydrophilic barrier layer on nanofibrous substrate as composite membrane via a facile route

Abstract In this work, a new strategy for fabrication of high flux thin film nanofibrous composite (TFNC) ultrafiltration membrane containing a hydrophilic barrier layer and a nanofibrous substrate was developed. Firstly, the double-layer nanofibrous mat containing very thin hydrophilic nanofiber top layer and nanofibrous supporting layer was manufactured via electrospinning technique. Then the hydrophilic nanofibrous top layer was remelted by suitable solvent vapor exposure and chemical crosslink in the crosslinking bath to form a barrier film on the supporting layer. Here, poly(vinyl alcohol) (PVA)/polyacrylonitrile (PAN) nanofibrous composite membranes were prepared by electrospinning of a very thin PVA nanofibrous layer with thickness of several micrometers on the electrospun PAN nanofibrous substrate, followed by remelting PVA nanofibrous layer to form a barrier PVA film by water vapor treatment and chemical crosslinking in glutaraldehyde water/acetone solution. The depositing time during PVA electrospinning and the water content of the crosslinking solution were utilized to control the thickness and the swelling degree of the PVA barrier layer. In this method, the shortcoming of easy penetration of the coating solution into the porous substrate in typical fabrication of surface coated anti-fouling composite membranes can be overcome, and the thickness of the barrier layer can be easily controlled by the depositing time of the PVA electrospinning. Filtration performances of the PVA/PAN composite membranes were evaluated by the oil/water emulsions separation system. The highest permeate flux of 210 l/m 2 h was achieved with the rejection of 99.5% for the composite membrane under the operating pressure of 0.3 MPa. It is believed that the strategy for fabricating TFNC membranes described here can be extended easily to fabricate nanofibrous composite membranes from many other polymeric materials simply by choosing the suitable solvent vapor treatment.

Effects of Degree of Cross-Links on Adhesion Curves of Cross-Linked Polymers Observed by a Point-Contact Method

The effects of degree of cross-links on the adhesion properties of polydimethylsiloxane (PDMS) were investigated with the use of a point-contact method in air at room temperature. The degree of cross-links, rho, was varied in a wide range, inducing changes in the rheology of the cross-linked PDMS from viscous solution to elastic gel, and the adhesion properties were examined by changing the separation velocity under a constant normal load and waiting period prior to separation. As a result, the adhesion force, F(A), strongly depended on rho and showed a maximum at a characteristic rho around the loss tangent (tan delta) = 1. In addition, the shapes of the adhesion curves were found to depend strongly on rho, and they were categorized into four types. The different states of cross-linked polymers, i.e., elastic-gel type, weak-gel type, and solution type, showed the different shapes. In the case of the weak gel, two types of characteristic adhesion curves were obtained, which resulted from the different separation mechanisms with and without cavitations near the surface due to the interface and cohesive failures. In the intermediate range of rho, viscous or elastic fingering was detected, which resulted in the characteristic shape of the adhesion curve. The factors determining the type of the adhesion curves are discussed in terms of the microscopic surface, bulk properties, and the different shapes of the adhesive front at the contact surface.

Stomach-Specific Controlled Release Gellan Beads of Acid-Soluble Drug Prepared by Ionotropic Gelation Method

The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using 3(2) factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful in H. pylori treatment.

Structure of calcium and zinc pectinate films investigated by FTIR spectroscopy

Calcium and zinc pectinate gels were prepared using a method which allowed calcium or zinc to diffuse from the cross-linking solution through a dialysis membrane to form a gel with amidated low-methoxyl pectin. The gel thus obtained was then dried, and the film structure was studied using FTIR spectroscopy as a function of the cation content (0%, 5%, 10%, and 15% w/v). Important consideration was given to the three functional groups (amide, carboxyl ester, and carboxylate groups) present in the pectin. When the zinc content was increased, the three wavenumber values corresponding to these three functional groups did not change significantly, while for calcium pectinate, the three wavenumber values were shifted profoundly when the amount of calcium ions changed. These results confirm that calcium ions could form stable interactions with carboxylate groups as described by the eggbox model [Grant, G.T.; Morris, E.R.; Rees, D.A.; Smith, P.J.C.; Tho, D. FEBS Lett. 1973, 32, 195–198] while the lower coordination number of zinc does not permit a structured gel to develop.

Development of a new controlled pesticide delivery system based on neem leaf powder

In order to minimize the agro-environmental pollution and health hazards caused by pesticides, in the present study, the neem leaf powder “(NLP)”, a bio-pesticide, has been exploited to develop the pesticide delivery devices. The presence of neem in the formulations along with the pesticide may enhance the potential of these systems due to its inherent pesticidal activity. We have prepared the NLP and alginate based beads by using CaCl 2 as crosslinker. To study the effect of composition of the beads on the release dynamics of fungicide (thiram), beads were prepared by varying the amount of NLP and crosslinker. The beads formed were characterized with Fourier transform infrared spectroscopy (FTIR), scanning electron micrograph (SEM), energy dispersion analysis by X-rays (EDAX), thermogravimetric analysis and swelling study. Formulation characteristics such as entrapment efficiency, bead size, percentage equilibrium swelling of the beads and diffusion mechanism for thiram release have been evaluated. Maximum (78.33 ± 2.89)% swelling has occurred in the beads prepared with 1.5% NLP, 2.5% alginate and 0.1 M crosslinker solution. In most of the formulations the values for the diffusion exponent ‘ n’ have been obtained >1 and hence the release of fungicides occurred through Case II diffusion mechanism.

Colon-specific delivery of resveratrol: Optimization of multi-particulate calcium-pectinate carrier

This study aimed at devising multi-particulate calcium-pectinate (Ca-pectinate) bead formulations for colon-targeted delivery of resveratrol. As Ca-pectinate beads were not sufficient to endure the upper GI environment and premature release of resveratrol occurred before their arrival to the colon, the beads were hardened by adding polyethyleneimine (PEI) in the cross-linking solution. The effects of PEI concentration, cross-linking time, and pectin to resveratrol ratio were investigated on beads’ characteristics, encapsulation efficiency, swelling–erosion, and resveratrol retention pattern of formulated beads. Proper conditions were optimized from these studies and optimized beads were further subjected to morphological examination. Formulated beads were spherical with ∼1 mm diameter. Addition of PEI to the cross-linking solution and a minimum cross-linking time were found to be crucial factors for colon-specific release of resveratrol. As PEI was added in the cross-linking solution, hardening of the bead surface occurred simultaneously with bead formation. Observations from the present study revealed that optimized Ca-pectinate beads hardened with PEI can efficiently encapsulate resveratrol and have potential for colon-specific delivery to the lower GI tract.

Effects of the molecular mass of tense-state polymerized bovine hemoglobin on blood pressure and vasoconstriction.

Despite recent advances in the design of hemoglobin (Hb)-based oxygen carriers (HBOCs), vasoconstriction, presumably caused by nitric oxide (NO) scavenging, vessel wall hyperoxygenation, and/or extravasation, has been identified as the principal road block hampering commercial development of HBOCs. This study was designed to analyze systemic and microvascular responses to the molecular mass and plasma concentration of tense (T)-state polymerized bovine Hb (PolybHb) solutions. Experiments were performed using the hamster window chamber model subjected to successive hypervolemic infusions of T-state PolybHb solutions. PolybHb plasma concentrations were evaluated, namely, 0.5, 1.0 and 1.5 g/dl, respectively. Infusion of PolybHb solutions with molecular mass >500 kDa elicited hypertension and vasoconstriction proportional to the plasma concentration and inversely proportional to the PolybHb cross-link density. However, two high-molecular mass PolybHb solutions, PolybHb(40:1)(high) PolybHb(50:1)(high), did not elicit vasoconstriction at all concentrations studied, whereas PolybHb(50:1)(high) only elicited moderate hypertension at the highest concentration studied. In contrast, infusion of PolybHb solutions with molecular mass <500 kDa elicited significant hypertension and vasoconstriction compared with PolybHb solutions with molecular mass >500 kDa that was proportional to the plasma concentration and inversely proportional to the PolybHb cross-link density. We present promising results for highly cross-linked T-state PolybHb solutions with molecular mass >500 kDa [PolybHb(40:1)(high) PolybHb(50:1)(high)], which supports the concept that HBOC size/molecular mass influences its proximity to the vascular endothelium and molecular diffusivity. The hemodynamics of HBOC within the plasma layer surrounding the abluminal side endothelium regulates NO production and consumption, vessel oxygen flux, and extravasation. Although mechanistically attractive, neither of these hypotheses can be directly tested in vivo and will require further investigation.

Intracoronary Injection of In Situ Forming Alginate Hydrogel Reverses Left Ventricular Remodeling After Myocardial Infarction in Swine

This study sought to determine whether alginate biomaterial can be delivered effectively into the infarcted myocardium by intracoronary injection to prevent left ventricular (LV) remodeling early after myocardial infarction (MI). Although injectable biomaterials can improve infarct healing and repair, the feasibility and effectiveness of intracoronary injection have not been studied. We prepared a calcium cross-linked alginate solution that undergoes liquid to gel phase transition after deposition in infarcted myocardium. Anterior MI was induced in swine by transient balloon occlusion of left anterior descending coronary artery. At 4 days after MI, either alginate solution (2 or 4 ml) or saline was injected selectively into the infarct-related coronary artery. An additional group (n = 19) was treated with incremental volumes of biomaterial (1, 2, and 4 ml) or 2 ml saline and underwent serial echocardiography studies. Examination of hearts harvested after injection showed that the alginate crossed the infarcted leaky vessels and was deposited as hydrogel in the infarcted tissue. At 60 days, control swine experienced an increase in left ventricular (LV) diastolic area by 44%, LV systolic area by 45%, and LV mass by 35%. In contrast, intracoronary injection of alginate (2 and 4 ml) prevented and even reversed LV enlargement (p < 0.01). Post-mortem analysis showed that the biomaterial (2 ml) increased scar thickness by 53% compared with control (2.9 +/- 0.1 mm vs. 1.9 +/- 0.3 mm; p < 0.01) and was replaced by myofibroblasts and collagen. Intracoronary injection of alginate biomaterial is feasible, safe, and effective. Our findings suggest a new percutaneous intervention to improve infarct repair and prevent adverse remodeling after reperfused MI.