Pore structure analysis of swollen dextran-methacrylate hydrogels by SEM and mercury intrusion porosimetry

The objectives of this study were to visually examine the surface and interior morphology of a new class of biodegradable hydrogels based on dextran-methacrylate and to quantify the porous structure of these hydrogels in swollen state. Two techniques (scanning electron microscopy and mercury intrusion porosimetry) were used to analyze pore structure of dextran-methacrylate hydrogels as a function of the degree of methacrylate substitution. SEM was used to observe 3-dimensional network structure of cryofixed and fractured swollen dextran-methacrylate hydrogels. Image analysis of the SEM data revealed different pore shapes and sizes, depending on the degree of substitution and the location within the hydrogel. A higher methacrylate-substituted dextran hydrogel showed a compact and rigid pore structure, while a lower substituted hydrogel showed a delicate and fragile pore structure. Mercury intrusion porosimetry analysis of the pore structure of dextran-methacrylate hydrogels provided useful and more reliable quantitative data of pore characteristics, such as total pore area, average pore diameter, their distribution, and bulk density. The total pore area and average pore diameter of swollen dextran-methacrylate hydrogels decreased with an increase in degree of methacrylate substitution, while bulk density increased with an increase in degree of substitution.     

Synthesis and characterization of dextran-maleic acid based hydrogel.

A new class of hydrogel precursor, dextran-maleic acid (Dex-MA), was synthesized by the reaction of dextran with maleic anhydride in the presence of the catalyst triethylamine. The effects of temperature, time, catalyst amount, and reactant concentration on the degree of substitution (DS) by MA was studied to establish an optimum reaction condition. The new hydrogel precursor had excellent solubility in various common organic solvents. The hydrogels based on Dex-MA precursor were made by the irradiation of Dex-MA with a long wave UV lamp. The Dex-MA hydrogels showed a very high swelling ratio in water, and the magnitude of swelling depended on the pH of the medium and the DS by MA. The Dex-MA hydrogels exhibited the highest swelling ratio in neutral pH, followed by acidic (pH 3) and alkaline pH (10). The most distinctive characteristic of Dex-MA hydrogels was that a carboxylic acid group was generated by the reaction of dextran with maleic anhydride. As a result, the swelling ratio increased with an increase of the DS of the MA segment (ionizable moiety that affects swelling ratio) in the Dex-MA hydrogel.     

Effect of solvent mixture on the properties of temperature- and pH-sensitive polysaccharide-based hydrogels

Novel partially biodegradable, temperature- and pH-sensitive polysaccharide-based hydrogels (NDF) were synthesized from modified dextran (dextran-maleic acid, Dex-MA) and N-isopropylacrylamide precursors over a wide range of mixed solvent ratios of dimethyl formamide (DMF) to water. N-Isopropylacrylamide monomers were chosen to impart thermo-responsive capability to Dex-MA, while Dex-MA was chosen to impart pH-responsive capability to N-isopropylacrylamide. The pH-sensitive precursor (Dex-MA) was synthesized by reacting dextran with maleic anhydride in the presence of triethylamine catalyst. To fabricate multi-stimuli hybrid hydrogel networks, both Dex-MA and N-isopropylarylamide precursors were photo-cross-linked via UV at a fixed Dex-MA to N-isopropylarylamide feed ratio over a wide range of DMF to water mixed solvent ratios. The newly synthesized PNIPAAm/Dex-MA hybrid hydrogels (NDF) were characterized by Fourier transform infrared spectroscopy for chemical structure determination, differential scanning calorimetry for thermal analysis and scanning electron microscopy for morphological study. The properties of the hybrid hydrogels, such as thermo-induced deswelling, pH-sensitivity, ionic strength sensitivity and thermo-reversibility, were also examined. The swelling data obtained clearly showed that newly synthesized multi-stimuli NDF hydrogels exhibited multi-responsive capability to external stimuli like temperature and pH. The morphological data obtained showed that this new class of PNIPAAm/Dex-MA hybrid hydrogels had a wide range of unique three-dimensional porous network structures that depended on the composition ratio of the mixed DMF/water solvent during cross-linking reaction. This unique but versatile 3D porous network structures of NDF hydrogels were correlated to the data from thermo-induced swelling behavior, thermo-reversibility, pH-dependent swelling and ionic strength sensitivity.     

Effect of solvent mixture on the properties of temperature- and pH-sensitive polysaccharide-based hydrogels

Novel partially biodegradable, temperature- and pH-sensitive polysaccharide-based hydrogels (NDF) were synthesized from modified dextran (dextran-maleic acid, Dex-MA) and N-isopropylacrylamide precursors over a wide range of mixed solvent ratios of dimethyl formamide (DMF) to water. N-Isopropylacrylamide monomers were chosen to impart thermo-responsive capability to Dex-MA, while Dex-MA was chosen to impart pH-responsive capability to N-isopropylacrylamide. The pH-sensitive precursor (Dex-MA) was synthesized by reacting dextran with maleic anhydride in the presence of triethylamine catalyst. To fabricate multi-stimuli hybrid hydrogel networks, both Dex-MA and N-isopropylarylamide precursors were photo-cross-linked via UV at a fixed Dex-MA to N-isopropylarylamide feed ratio over a wide range of DMF to water mixed solvent ratios. The newly synthesized PNIPAAm/Dex-MA hybrid hydrogels (NDF) were characterized by Fourier transform infrared spectroscopy for chemical structure determination, differential scanning calorimetry for thermal analysis and scanning electron microscopy for morphological study. The properties of the hybrid hydrogels, such as thermo-induced deswelling, pH-sensitivity, ionic strength sensitivity and thermoreversibility, were also examined. The swelling data obtained clearly showed that newly synthesized multi-stimuli NDF hydrogels exhibited multi-responsive capability to external stimuli like temperature and pH. The morphological data obtained showed that this new class of PNIPAAm/Dex-MA hybrid hydrogels had a wide range of unique three-dimensional porous network structures that depended on the composition ratio of the mixed DMF/water solvent during cross-linking reaction. This unique but versatile 3D porous network structures of NDF hydrogels were correlated to the data from thermo-induced swelling behavior, thermo-reversibility, pH-dependent swelling and ionic strength sensitivity.     

In vitro release behavior of dextran-methacrylate hydrogels using doxorubicin and other model compounds

In vitro drug release behavior of doxorubicin, Alizarin Red S, FITC-dextran from photocross-linked dextran-methacrylate hydrogel was studied. The effects of pH of media, degree of substitution (DS) of dextran-methacrylate hydrogel, and molecular weight of model compounds on their release profiles were investigated. Each model compound was successfully incorporated into dextran-methacrylate hydrogel matrix through photopolymerization of the hydrogel precursor. Delayed release of model compounds was observed with these hydrogels having a higher DS. Doxorubicin and Alizarin Red S showed pH-dependent release behavior because of the presence of ionizable groups in their structure. Different types of ionization of doxorubicin and Alizarin Red S resulted in more release into an acidic or alkaline media. As molecular weights of drugs increased, the total amount of released drug at the end of 240 hrs decreased significantly and reached a minimum level as the MW of drugs reached about 10,000. Release of these three model compounds followed simple Fickian diffusion at an early stage of release, i.e., cumulative release of model compounds was proportional to the square root of time. Dextran-methacrylate hydrogel effectively delayed and controlled the release of anticancer antibiotics, doxorubicin.     

pH- and Temperature-Responsive P(DMAEMA-GMA)-Alginate Semi-IPN Hydrogels Formed by Radical and Ring-Opening Polymerization for Aminophylline Release

A novel poly((2-dimethylamino) ethyl methacrylate-glycidyl methacrylate)-alginate (P(DMAEMA-GMA)alginate) semi-IPN hydrogel was synthesized via radical polymerization of the double bonds and ring-opening of the epoxy groups without using catalyst and cross-linker. ¹H-NMR, FT-IR and DSC data were consistent with the expected structures for the hydrogels. The interior morphology of the hydrogels was also investigated by SEM. The swelling ratio and compressive strength of the hydrogels were measured. The semi-IPN hydrogel had pH and temperature sensitivity, and pH-sensitive points of all hydrogels were found to be at pH 5.0. The release behavior of the model drug, aminophylline, was found to be dependent on the hydrogel composition and environment pH, which manifests that these materials have potential applications as intelligent drug carriers.     

Synthesis and characterization of partially biodegradable, temperature and pH sensitive Dex-MA/PNIPAAm hydrogels

The objective of the study is to impart temperature and pH-sensitive capabilities to polysaccharide-based hydrogels, so that they can change their swelling property upon external stimulation like temperature or/and pH. Dextran was chosen as the model polysaccharide compound for such a demonstration. A novel class of dextran-maleic anhydride (Dex-MA)/poly(N-isopropylacrylamide) hybrid hydrogels was designed and synthesized by UV photocrosslinking. The dextran-based precursor (Dex-MA) was prepared by substituting the hydroxyl groups in Dex by MA. This Dex-MA precursor was then photocrosslinked with a known temperature sensitive precursor (N-isopropylacrylamide, NIPAAm) to form hybrid hydrogels having a wide range of composition ratio of Dex-MA to NIPAAm precursors. Due to the biodegradable nature of dextran, these Dex-MA/PNIPAAm hybrid hydrogels are partially biodegradable. These smart hybrid hydrogels were characterized by Fourier transform infrared spectroscopy for structural determination, differential scanning calorimertry for thermal property, maximum swelling ratio, swelling kinetics, temperature response kinetics, and effect of pH. The data obtained clearly show that these new smart hybrid hydrogels were responsive to the external changes of temperature as well as pH. The magnitude of smart and hydrogel properties of these hybrid hydrogels were found to depend on the feed composition ratio of the two precursors. By changing the composition ratio of these two precursors, the phase transition temperature (lower critical solution temperature) of the hybrid hydrogels could also be adjusted to be or near the body temperature for the potential applications in bioengineering and biotechnology fields.     

Biocatalytic synthesis of highly ordered degradable dextran-based hydrogels

We have prepared unique macroporous and ordered dextran-based hydrogels using a single-step biocatalytic transesterification reaction between dextran and divinyladipate in neat dimethylsulfoxide. These hydrogels show a unimodal distribution of interconnected pores with average diameters from 0.4 to 2.0 microm depending on the degree of substitution. In addition, the hydrogels show a higher elastic modulus for a given swelling ratio than chemically synthesized dextran-based hydrogels. In vivo studies in rats show that the hydrogel networks are degradable over a range of time scales from 5 to over 40 days, and possess good biocompatibility, as reflected in only a mild inflammatory reaction and minor fibrous capsule formation during the time-frame of subcutaneous implantation. These combined properties may offer competitive advantages in biomedical applications ranging from tissue engineering to controlled drug delivery.     

Hydrogel based on interpenetrating polymer networks of dextran and gelatin for vascular tissue engineering

Hydrogel networks are highly desirable as three-dimensional (3-D) tissue engineering scaffolds for cell encapsulation due to the high water content and ability to mimick the native extracellular matrix. However, their application is limited by their nanometer-scale mesh size, which restricts the spreading and proliferation of encapsulated cells, and their poor mechanical properties. This study seeks to address both limitations through application of a novel cell-encapsulating hydrogel family based on the interpenetrating polymer network (IPN) of gelatin and dextran bifunctionalized with methacrylate (MA) and aldehyde (AD) (Dex-MA-AD). The chemical structure of the synthesized Dex-MA-AD was verified by (1)H-NMR and the degrees of substitution of MA and AD were found to be 14 and 13.9+/-1.3 respectively. The water contents in all these hydrogels were approximately 80%. Addition of 40 mg/ml to 60 mg/ml gelatin to neat Dex-MA-AD increased the compressive modulus from 15.4+/-3.0 kPa to around 51.9+/-0.1 kPa (about 3.4-fold). Further, our IPN hydrogels have higher dynamic storage moduli (i.e. on the order of 10(4)Pa) than polyethylene glycol-based hydrogels (around 10(2)-10(3)Pa) commonly used for smooth muscle cells (SMCs) encapsulation. Our dextran-based IPN hydrogels not only supported endothelial cells (ECs) adhesion and spreading on the surface, but also allowed encapsulated SMCs to proliferate and spread in the bulk interior of the hydrogel. These IPN hydrogels appear promising as 3-D scaffolds for vascular tissue engineering.     

Swellable coatings for hearing aid applications

The problem of acoustic feedback in hearing aids could be solved potentially by applying a compliant hydrogel to the outer surface that would conform to the ear canal and block feedback. With this objective, several formulations of hydrogels were developed and their swelling and mechanical properties investigated. Hydrogel formulations were polymerized from hydroxyethyl methacrylate (HEMA) and N-vinyl-pyrrolidone (NVP), with various photo-initiators, crosslinkers, and swelling agents. The hydrogel that swelled most rapidly and yet remained undissolved in water had a monomer composition of 40 mol% HEMA, 60 mol% NVP, with 1 wt% polyethylene glycol dimethacrylate as a crosslinker, and 0.5 wt% 2,2-dimethoxy-2-phenyl-acetophenone as the photo-initiator. The tensile modulus, strength, hardness, and durability of the dry hydrogels were not a strong function of composition. In the swollen state, the mechanical properties were much reduced. The potential use of these materials on hearing aids has been discussed in this article.     

Preparation of poly(2-glucosyloxyethyl methacrylate)-concanavalin A complex hydrogel and its glucose-sensitivity

A glucose-sensitive hydrogel was prepared by introducing concanavalin A (Con. A) into poly(2-glucosyloxyethyl methacrylate) (poly(GEMA)) hydrogel. The decrease in swelling ratio and increase in crosslinking density by introduction of Con. A into the poly(GEMA) hydrogel indicate that the complexation introduces additional crosslinking points. The swelling of the hydrogel increased in the presence of glucose, and the swelling ratio was dependent on the glucose concentration. The glucose sensitivity of the hydrogel is attributable to the dissociation of the complex between poly(GEMA) and Con. A in the presence of glucose. Furthermore, the poly(GEMA)-Con. A complex hydrogel was responsive to the kind of monosaccharide; its swelling ratio was changed by the presence of glucose or mannose, but not by the presence of galactose. The swelling properties of this hydrogel might be useful for the development of a glucose-sensitive device.     

Structural analysis of dextran-based hydrogels obtained chemoenzymatically

This work reports the results of structural analysis in novel dextran-acrylate (dexT70-VA) hydrogels generated chemoenzymatically. Porous structure as well as hydrogel surface and interior morphologies were evaluated by mercury intrusion porosimetry (MIP), nitrogen adsorption (NA), and scanning electron microscopy (SEM) analyses, as a function of the degree of substitution (DS), and initial water content used in the preparation of the hydrogel. MIP analysis showed that the overall networks were clearly macroporous with pore sizes ranging from 0.065 to 10 microm. As expected, the average pore size decreased as DS increased and as initial water content decreased. Moreover, the porosity values ranged from 75 up 90%, which shows that these hydrogels present an interconnected pore structure. Nitrogen adsorption analyses showed that the specific surface area of dexT70-VA hydrogels increased either by increasing the DS or by decreasing the initial water content of the hydrogel. SEM results revealed that the surface of hydrogels with lower DS presented either a porous structure or a polymeric "skin" covering the pores, whereas hydrogels with higher DS were totally porous. Furthermore, the interior morphology varied according to the DS and the initial water content of the hydrogels. Finally, the average pore size was also determined from the swelling of hydrogel using a theoretical model developed by Flory-Rehner. The comparison of the SEM and MIP results with the ones obtained by the equilibrium swelling theory of Flory-Rehner shows that this approach highly underestimates the average pore size.     

甲基丙烯酸钠修饰光交联海藻酸盐水凝胶支架的制备和表征

文题释义：甲基丙烯酸钠：是一种具有双功能的化学基团的有机小分子,一端含有2-甲基丙烯酰基,该基团具有良好的化学活性,可与化合物中的多种基团反应而修饰化合物;另一个功能集团就是拥有负电荷基团,能给修饰过的化合物材料表面带来稳定的负电荷。 光引发剂：又称光敏剂,是一类能在紫外光区(250-420 nm)或可见光区(400-800 nm)吸收一定波长的能量,产生自由基、阳离子等,从而引发单体聚合交联固化的化合物。引发剂分子在紫外光区(250-400 nm)或可见光区(400-800 nm)有一定吸光能力,在直接或间接吸收光能后,引发剂分子从基态跃迁到激发单线态,经系间窜跃至激发三线态;在激发单线态或三线态经历单分子或双分子化学作用后,产生能够引发单体聚合的活性碎片,这些活性碎片可以是自由基、阳离子、阴离子等。按照引发机制不同,光引发剂可分为自由基聚合光引发剂与阳离子光引发剂,其中以自由基聚合光引发剂应用最为广泛。 背景：光交联海藻酸盐水凝胶因具有良好的生物相容性、可微创注射等优势已为热门的组织工程研究材料,但是仍然存在强度不足、细胞黏附能力不足等问题。 目的：构建载负电荷的光交联海藻酸盐水凝胶材料,探索其物理性能和细胞黏附性能变化。 方法：利用海藻酸钠和2-氨乙基甲基丙烯酸酯盐酸盐制备甲基丙烯酸酯化海藻酸盐后,再与光引发剂和不同浓度甲基丙烯酸钠(0,20,40,60 mmol/L)混合制备载负电荷光交联海藻酸盐水凝胶,利用傅里叶红外光谱仪分析水凝胶的功能基团变化情况,扫面电镜观察水凝胶的表面形态,并测量其溶胀率。将MC3T3-E1细胞与各组水凝胶共培养48 h,采用活死染色与CCK-8法分析水凝胶的细胞毒性;接种MC3T3-E1细胞于4组水凝胶表面,在第4小时活死染色观察细胞早期黏附情况,第3天活死染色观察细胞伸展情况。 结果与结论：①傅里叶红外光谱分析显示,甲基丙烯酸钠的引入可在水凝胶红外波普波数1 600 cm^-1左右处出现来自甲基丙烯酸钠的新波峰;②扫描电镜显示随着甲基丙烯酸钠浓度的增加,光交联海藻酸盐水凝胶的致密度增加,孔径减小;③溶胀率测试显示随着甲基丙烯酸钠浓度的升高,光交联海藻酸盐水凝胶的溶胀率逐渐降低;④活死染色显示4种水凝胶表面的细胞生长状态良好,细胞活性均在95%以上;CCK-8检测显示,载负电荷的光交联海藻酸盐水凝胶材料无细胞毒性;⑤随着甲基丙烯酸钠引入量的增加,载负电荷光交联海藻酸盐水凝胶表面的早期细胞黏附率逐渐增加,细胞伸展状态明显改善;⑥结果表明,甲基丙烯酸钠修饰的引入调节了光交联海藻酸盐水凝胶物理性能,并明显提高了其细胞黏附性能。 ORCID: 0000-0002-1054-6002(赵德路) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Arginine-based polyester amide/polysaccharide hydrogels and their biological response

An advanced family of biodegradable cationic hybrid hydrogels was designed and fabricated from two precursors via a UV photocrosslinking in an aqueous medium: unsaturated arginine (Arg)-based functional poly(ester amide) (Arg-UPEA) and glycidyl methacrylate chitosan (GMA-chitosan). These Arg-UPEA/GMA-chitosan hybrid hydrogels were characterized in terms of their chemical structure, equilibrium swelling ratio (Q_eq), compressive modulus, interior morphology and biodegradation properties. Lysozyme effectively accelerated the biodegradation of the hybrid hydrogels. The mixture of both precursors in an aqueous solution showed near non-cytotoxicity toward porcine aortic valve smooth muscle cells at total concentrations up to 6 mg ml⁻¹. The live/dead assay data showed that 3T3 fibroblasts were able to attach and grow on the hybrid hydrogel and pure GMA-chitosan hydrogel well. Arg-UPEA/GMA-chitosan hybrid hydrogels activated both TNF-α and NO production by RAW 264.7 macrophages, and the arginase activity was also elevated. The integration of the biodegradable Arg-UPEA into the GMA-chitosan can provide advantages in terms of elevated and balanced NO production and arginase activity that free Arg supplement could not achieve. The hybrid hydrogels may have potential application as a wound healing accelerator.     

聚甲基丙烯酸羟乙酯水凝胶人工晶状体材料的合成与性能

以甲基丙烯酸羟乙酯为原料,过硫酸铵/偏重亚硫酸钠为引发体系,二甲基丙烯酸三乙二醇酯为交联剂,采用溶液聚合法制备了聚甲基丙烯酸羟乙酯水凝胶(PHEMA)人工晶状体材料。系统考察了聚合反应时间、温度及引发剂和交联剂的用量等对该水凝胶材料机械强度、平衡水含量(EWC)的影响,并对PHEMA水凝胶的结构和光学性能进行了表征。实验结果表明,PHEMA水凝胶的最佳合成条件为:引发剂0.5wt%,交联剂1.0wt%,反应温度40℃,反应时间36h。在此条件下制备的PHEMA水凝胶的拉伸强度达到0.57MPa,邵氏A硬度为23.0,平衡含水量超过40%,透光率≥97%。     

Modeling the controllable pH-responsive swelling and pore size of networked alginate based biomaterials

Semisynthetic network alginate polymer (SNAP), synthesized by acetalization of linear alginate with di-aldehyde, is a pH-responsive tetrafunctionally linked 3D gel network, and has potential application in oral delivery of protein therapeutics and active biologicals, and as tissue bioscaffold for regenerative medicine. A constitutive polyelectrolyte gel model based on non-Gaussian polymer elasticity, Flory–Huggins liquid lattice theory, and non-ideal Donnan membrane equilibria was derived, to describe SNAP gel swelling in dilute and ionic solutions containing uni-univalent, uni-bivalent, bi-univalent or bi-bi-valent electrolyte solutions. Flory–Huggins interaction parameters as a function of ionic strength and characteristic ratio of alginates of various molecular weights were determined experimentally to numerically predict SNAP hydrogel swelling. SNAP hydrogel swells pronouncedly to 1000 times in dilute solution, compared to its compact polymer volume, while behaving as a neutral polymer with limited swelling in high ionic strength or low pH solutions. The derived model accurately describes the pH-responsive swelling of SNAP hydrogel in acid and alkaline solutions of wide range of ionic strength. The pore sizes of the synthesized SNAP hydrogels of various crosslink densities were estimated from the derived model to be in the range of 30–450 nm which were comparable to that measured by thermoporometry, and diffusion of bovine serum albumin. The derived equilibrium swelling model can characterize hydrogel structure such as molecular weight between crosslinks and crosslinking density, or can be used as predictive model for swelling, pore size and mechanical properties if gel structural information is known, and can potentially be applied to other point-link network polyelectrolytes such as hyaluronic acid gel.     

Synthesis of 1-Octadecanol-Modified Water-Swelling Polyurethane Hydrogels as Vaginal Drug-Delivery Vehicle

The purpose of this work was to develop a novel polyurethane hydrogel system for sustained drug release, which could be used as a vaginal drug-delivery vehicle. The blank polyurethane hydrogels were synthesized by a polyol oligomeric, a diisocyanate and a triol (used as cross-linking agent). In order to improve the swelling ability of a polyurethane hydrogel, a small amount of 1-octadecanol was added. Additionally, the structure, mechanical properties and thermal properties of polymers were assessed by FT-IR, WAXD, DSC and mechanical tests. The results show that no more than 2.5 wt% of 1-octadecanol additives is sufficient to affect the release profile without changing the structure and mechanical properties of the polyurethane hydrogels obviously. Tinidazole was chosen as a model drug, the release data of drug from polyurethane hydrogels were fitted using the Ritger–Peppas equation and the result showed that it was non-Fickian diffusion, which means that the drug release was controlled by both swollen control and diffusion control. In conclusion, our work proves that the synthesized polyurethane hydrogel modified by 1-octadecanol may be a promising sustained release drug carrier.     

Synthesis,characterization and cytotoxicity of photo-crosslinked maleic chitosan–polyethylene glycol diacrylate hybrid hydrogels

Synthetic hydrogels are important biomaterials for many biomedical applications and hydrogels produced via photo-gelation have shown particular promise. In this paper, we describe a new family of biodegradable hybrid hydrogels fabricated in aqueous solution via long wavelength UV photo-crosslinking using maleic chitosan and polyethylene glycol diacrylate (PEGDA) as precursors. The maleic chitosan precursor was prepared by a simple one-step chemical modification of chitosan, with high yields, and characterized by Fourier transform infrared spectroscopy, ¹H NMR and ¹³C NMR. Maleic chitosan and PEGDA precursors at a wide range of weight feed ratios were mixed in aqueous solution and directly photo-crosslinked for 10 min under a long wavelength UV light (365 nm) using 4-(2-hydroxyethoxy) phenyl-(2-hydroxy-2-propyl) ketone (Irgacure 2959) as photoinitiator. It was observed that as the weight feed ratio of maleic chitosan to PEGDA decreased the pore sizes of the hydrogel samples decreased, thereby increasing the densities of the hydrogel networks and producing a lower swelling ratio and a higher compressive modulus. The molecular weight of PEGDA had a similar effect. Preliminary cell cytotoxicity tests of both the maleic chitosan precursor and maleic chitosan/PEGDA hydrogels, based on the MTT assay and live–dead assay, respectively, showed that these new chitosan-based biodegradable biomaterials were relatively non-toxic to bovine aortic endothelial cells at low dosages.     

Hydrogel probe for iontophoresis drug delivery to the eye

The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm² for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. Iontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.     

Hydrogel probe for iontophoresis drug delivery to the eye

The aim of this study was to evaluate the use of a solid hydrogel loaded with a drug solution as a probe for ejecting drugs to the eye upon application of low current iontophoresis. Hydroxyethyl methacrylate (HEMA), cross-linked with ethylene glycol dimethacrylate (EGDMA), and cross-linked arabinogalactan or dextran were prepared to form solid hydrogels. The hydrogels were examined for their mechanical suitability, absorption of drug solution and in vitro release properties when applying an iontophoretic current through the drug-loaded hydrogel into a solid-agar surface. Transconjunctival and transscleral iontophoresis of gentamicin sulfate was studied in healthy rabbits using drug-loaded disposable HEMA hydrogel disc probes. Gentamicin concentrations in different eye segments were assayed using a fluorescence polarization immunoassay. Preliminary corneal toxicity was examined in rabbits using a current intensity of 2.5 and 5.1 mA/cm2 for 60 and 120 s. The most appropriate hydrogel is composed of HEMA, 2% EGDMA and 75% water. lontophoresis onto agar gel was found indicative for the evaluation of iontophoretic activity of a hydrogel. Transscleral iontophoretic treatment resulted in high concentrations of drugs in the posterior segments of the eye. Application of iontophoresis onto the rabbit eye caused a reversible swelling of the cornea which lasted a few hours after application. Low current iontophoresis using drug-loaded hydrogel has a potential clinical value in obtaining high drug concentration at posterior segments of the eye.