HEMA-based Hydrogels Research Articles

Evaluation of photopolymerizable hema-based hydrogels for release of anti-diabetic drug metformin HCl

Evaluation of photopolymerizable hema-based hydrogels for release of anti-diabetic drug metformin HCl

Radiolytic synthesis of gold nanoparticles in HEMA-based hydrogels: Potentialities for imaging nanocomposites

Abstract This article reports on the radiolytic synthesis of nanocomposites containing gold nanoparticles (AuNPs) within two types of hydrogels based on 2-hydroxyethyl methacrylate (HEMA): (i) plain networks with various contents in ethylene glycol dimethacrylate (EGDMA), as a cross-linker and (ii) stimuli-responsive (SR) networks prepared from these monomers copolymerized with [2-(methacryloyloxy)ethyl]trimethylammonium chloride (MADQUAT) to confer pH-switchable swelling. Hydrogels were prepared by photopolymerization with well-defined composition and a high degree of monomer conversion using two experimental procedures, as xerogels or in aqueous solution. Besides MADQUAT, acrylic acid (AA) or N-isopropylacrylamide have been tested as copolymers, yielding pHor temperature-sensitive hydrogels, respectively. Isothermal swelling in water was affected by monomer composition. Electron beam (EB) irradiation at doses up to 100 kGy of poly(HEMA) xerogels and water-swollen networks prepared with 0.5 wt% of EGDMA had a moderate impact on swelling characteristics and thermomechanical properties of the plain materials, whereas small amounts of extractables were formed. Poly(HEMA)-based nanocomposites containing AuNPs were successfully obtained by EB irradiation of samples swollen by aqueous solutions of Au(III). The effects of dose and cross-linking density on the formation of AuNPs were monitored by UV-visible spectroscopy. Irradiation at well-defined temperatures of the Au(III)-loaded SR hydrogels induced the formation of nanoparticles with size-dependent features, whereas the efficiency of Au(III) reduction at 10 kGy was not significantly affected by the network structure. EB-induced reduction of Au(III) in poly(HEMA) hydrogels using a lead mask to generate well-defined patterns yielded coloured and long-lasting images in the zones where the nanocomposite was formed.

Polylactide/polyethylene glycol fibrous mats for local paclitaxel delivery: comparison of drug release into liquid medium and to HEMA-based hydrogel model

2-Hydroxyethyl methacrylate (HEMA) hydrogels containing 37% water were prepared to investigate the release of hydrophobic anticancer drug paclitaxel (PTX) from electrospun polylactide (PLA) fibrous mats. The impact of the incorporated amphiphilic polyethylene glycol (PEG) on the drug release was also studied. The release profiles were investigated in various arrangements and compared to release into aqueous media. The nanofibers with added PEG released significantly higher amounts of paclitaxel and for longer time period compared to fibers containing only the hydrophobic drug. When compared various release conditions, significantly higher amount of paclitaxel released to hydrogel compared to aqueous media. HEMA-based hydrogel was found to better approximate in vivo conditions in comparison with commonly used liquid media.

Hydrogel implants for transscleral drug delivery for retinoblastoma treatment.

Retinoblastoma (Rb) is the most common primary malignant intraocular tumor in children which develops from the retinal stem cells. Systemic chemotherapy is the typical therapeutic treatment and though most children survive Rb, they often lose their vision, or the eye needs to be enucleated. Regarding to the pure availability of the target tumor by systemic chemotherapy, the local anticancer drug administration would be advantageous to increase the local drug concentration and minimize adverse side effects of chemotherapy. The present paper describes a new hydrogel implant enabled to deliver therapeutically active doses of low molecular weight hydrophilic antitumor drugs topotecan and vincristine. The hydrogel implant is proposed as bi-layered with an inner hydrophilic layer from 2-hydroxyethyl methacrylate (HEMA) serving as a reservoir of the chemotherapeutic agent and an outer hydrophobic layer from 2-ethoxyethyl methacrylate (EOEMA) acting as a barrier to protect the surrounding vascularized tissue against cytotoxicity of the delivered chemotherapeutics. The experiments with enucleated pig eyes demonstrated the ability of tested drugs to diffuse through sclera and reach the vitreous humor. HEMA-based hydrogels were examined in terms of sorption, release and transport properties, showing the possibility of adjusting the loading capacity and diffusion of the drugs by the degree of crosslinking. The EOEMA-based gels proved to be an inert for drug sorption and diffusion. A chorioallantoic membrane assay demonstrated excellent biocompatibility of unloaded hydrogels, and in vitro experiments confirmed significant cytotoxicity of drug-loaded hydrogels against a Rb cell line; 2 days for those topotecan-loaded and a minimum of 6 days for vincristine-loaded hydrogels. The bi-layered hydrogel implant can be considered promising for local administration of active agents to eye-globe for the treatment of Rb and also other ocular disorders.

Importance of zwitterionic incorporation into polymethacrylate-based hydrogels for simultaneously improving optical transparency, oxygen permeability, and antifouling properties.

Conventional 2-hydroxyethyl methacrylate (HEMA)-based hydrogels have an inverse relationship between optical transparency (OP) and oxygen permeability (Dk) as a function of water content. While the higher water content favors the oxygen permeability of HEMA-based hydrogels, it also causes poor optical transparency due to the water-induced scattering center effect. Here, we propose and demonstrate that the incorporation of zwitterionic [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA) with HEMA hydrogels enables the achievement of both properties (OP = 98% and Dk = 54.7) in hydrogels at high water contents of 84%, and both values are much higher than those of pure HEMA hydrogels (OP = 2.3% and Dk = 17.5 barriers). HEMA-SBMA hydrogels are crosslinked by electrostatic interactions between the zwitterionic SBMA groups and hydrogen bonds between the HEMA groups. The introduction of SBMA into HEMA not only increases the quantity and quality of strongly binding water inside the networks, but also affects the porous structure of the gels, both of which are correlated with OP and Dk. Moreover, hybrid HEMA-SBMA hydrogels demonstrate their excellent antifouling function to prevent nonspecific protein adsorption in vitro, as well as their biocompatibility and hemocompatibility when implanted in mice in vivo. A combination of these excellent properties of HEMA-SBMA hydrogels (high water content, high optical transparency, high oxygen permeability, good antifouling function, and low foreign-body reaction) makes them highly promising for contact lens-based ophthalmic applications. This work, in line with our other HEMA-CBMA hydrogels, offers a new strategy to design hybrid hydrophilic-zwitterionic materials for improving their multi-faceted properties of interest, beyond the conventional designs of hydrophilic-hydrophilic and hydrophilic-hydrophobic materials.

Synthesis, Swelling Properties and Evaluation of Genotoxicity of Hydrogels Based on (Meth)acrylates and Itaconic Acid

In this study we prepared hydrogels based on 2-hydroxyethyl methacrylate (HEMA): PHEMA homopolymer and two terpolymers of HEMA, itaconic acid (IA) and two poly(alkylene glycol) (meth) acrylates (PAGM): poly(ethylene glycol)6 acrylate (P(HEMA/IA/PAGM1)) and poly(propylene glycol)5 methacrylate (P(HEMA/IA/PAGM2)). Hydrogels were synthesized by gamma-irradiated radical polymerization and subjected to swelling measurements and genotoxicity evaluation. Swelling studies confirmed that these hydrogels deserve consideration as biomaterials due to their ability to swell in phosphate buffer but maintaining physical integrity for a prolonged contact time after equilibrium state has been reached. Comet assay showed certain genotoxic effect following cell exposure to extracts of hydrogels, which was dependent on the concentration of extracts, chemical composition of hydrogels and the degree of crosslinking. The influence of concentration on genotoxicity was the most pronounced. The synthesis of these novel HEMA-based hydrogels should be optimized so as to reduce their toxicity and enable the use in clinical practice.

Improving hydrogels׳ toughness by increasing the dissipative properties of their network

The weak mechanical performance and fragility of hydrogels limit their application as biomaterials for load bearing applications. The origin of this weakness has been explained by the low resistance to chains breakage composing the hydrogel and to the cracks propagation in the hydrogel submitted to loading conditions. These low resistance and crack propagation were in turn related to an insufficient energy dissipation mechanism in the hydrogel structure. The goal of this study is to evaluate the dissipation mechanism in covalently bonded hydrogels so that tougher hydrogels can be developed while keeping for the hydrogel a relatively high mechanical stiffness. By varying parameters such as cross-linker type or concentration as well as water ratio, the dissipative properties of HEMA-based hydrogels were investigated at large deformations. Different mechanisms such as special friction-like phenomena, nanoporosity, and hydrophobicity were proposed to explain the dissipative behavior of the tested hydrogels. Based on this analysis, it was possible to develop hydrogels with increased toughness properties.

Tandem ATRP/Diels–Alder synthesis of polyHEMA-based hydrogels

An efficient controlled process for the preparation of HEMA-based hydrogels by means of the Diels–Alder reaction.

External Ocular Surface and Lens Microbiota in Contact Lens Wearers With Corneal Infiltrates During Extended Wear of Hydrogel Lenses

To determine whether carriage of microbes on the contact lens or ocular surfaces during extended wear (EW) with soft hydroxyethyl methacrylate (HEMA)-based contact lenses predisposes the wearer to adverse events. Participants (non-contact lens wearers) were enrolled in a clinical study involving wear of HEMA-based hydrogel lenses on a six night EW basis with weekly replacement. Type and number of bacteria colonizing the lower lid margins, upper bulbar conjunctiva, and contact lenses during EW after one night, 1 week, 1 month, and thereafter every 3 months for 3.5 years were determined. The association of bacteria with adverse responses was compared between carriers (defined as having significant microbes cultured from two or more samples with 1 year) and noncarriers, and the strength of the association was estimated using multivariate logistic regression. Carriers of gram-positive bacteria on lenses (particularly coagulase negative staphylococci or Corynebacterium spp.) were approximately three and eight times more likely to develop contact lens-induced peripheral ulcers (CLPUs) and asymptomatic infiltrates (AIs), respectively. Staphylococcus aureus was most frequently isolated from lenses during CLPU. Carriers of gram-negative bacteria on lenses were five times more likely to develop contact lens-induced acute red eye (CLARE). Haemophilus influenzae was isolated most frequently from lenses during CLARE and AI events. Bacterial carriage on contact lenses during EW predisposes the wearer to the development of corneal inflammatory events including CLARE, CLPU, and AI.

Macroporous hydrogels based on 2-hydroxyethyl methacrylate. Part 6: 3D hydrogels with positive and negative surface charges and polyelectrolyte complexes in spinal cord injury repair

Macroporous hydrogels are artificial biomaterials commonly used in tissue engineering, including central nervous system (CNS) repair. Their physical properties may be modified to improve their adhesion properties and promote tissue regeneration. We implanted four types of hydrogels based on 2-hydroxyethyl methacrylate (HEMA) with different surface charges inside a spinal cord hemisection cavity at the Th8 level in rats. The spinal cords were processed 1 and 6 months after implantation and histologically evaluated. Connective tissue deposition was most abundant in the hydrogels with positively-charged functional groups. Axonal regeneration was promoted in hydrogels carrying charged functional groups; hydrogels with positively charged functional groups showed increased axonal ingrowth into the central parts of the implant. Few astrocytes grew into the hydrogels. Our study shows that HEMA-based hydrogels carrying charged functional groups improve axonal ingrowth inside the implants compared to implants without any charge. Further, positively charged functional groups promote connective tissue infiltration and extended axonal regeneration inside a hydrogel bridge.

Qualitative and quantitative characterization of the in vitro dehydration process of hydrogel contact lenses

To investigate the in vitro dehydration process of conventional hydrogel and silicone-hydrogel contact lens materials. Eight conventional hydrogel and five silicone-hydrogel contact lenses were dehydrated under controlled environmental conditions on an analytical balance. Data were taken at 1-min intervals and dehydration curves of cumulative dehydration (CD), valid dehydration (VD), and dehydration rate (DR) were obtained. Several quantitative descriptors of the dehydration process were obtained by further processing of the information. Duration of phase I (r(2) = 0.921), CD at end of phase I (r(2) = 0.971), time to achieve a DR of -1%/min (r(2) = 0.946) were strongly correlated with equilibrium water content (EWC) of the materials. For each individual sample, the VD at different time intervals can be accurately determined using a 2nd order regression equation (r(2) > 0.99 for all samples). The first 5 min of the dehydration process show a relatively uniform average CD of about -1.5%/min. After that, there was a trend towards higher average CD for the following 15 min as the EWC of the material increases (r(2) = 0.701). As a consequence, average VD for the first 5 min displayed a negative correlation with EWC (r(2) = 0.835), and a trend towards uniformization among CL materials for the following periods (r(2) = 0.014). Overall, silicone-hydrogel materials display a lower dehydration, but this seems to be primarily due to their lower EWC. DR curves under the conditions of the present study can be described as a three-phase process. Phase I consists of a relatively uniform DR with a duration that ranges from 10 to almost 60 min and is strongly correlated with the EWC of the polymer as it is the CD during this phase. Overall, HEMA-based hydrogels dehydrate to a greater extent and faster than silicone-hydrogel materials. There are differences in water retention between lenses of similar water content and thickness that should be further investigated.

Effect of phosphate functional groups on the calcification capacity of acrylic hydrogels

The incorporation of negatively charged groups into the structure of synthetic polymers is frequently advocated as a method for enhancing their calcification capacity required in orthopedic and dental applications. However, the results reported by various research groups are rather contentious, since inhibitory effects have also been observed in some studies. In the present study, phosphate groups were introduced in poly(2-hydroxyethyl methacrylate) (PHEMA) by copolymerization with 10% mol of either mono(2-acryloyloxyethyl) phosphate (MAEP) or mono(2-methacryloyloxyethyl) phosphate (MMEP). Incubation of these hydrogels for determined durations (1–9 weeks) in a simulated body fluid (SBF) solution induced deposition of calcium phosphate (CaP) deposits of whitlockite type. After 9 weeks, the amount of calcium deposited on the phosphate-containing polymers was four times lower than that found on PHEMA, as determined by X-ray photoelectron spectroscopy (XPS). Samples of copolymer HEMA–MAEP were implanted subcutaneously in rats and evaluated after 9 weeks. No CaP deposits could be detected on the copolymer by XPS or energy dispersive X-ray spectroscopy, while PHEMA samples were massively calcified. It was concluded that the presence of phosphate groups decreased the calcification capacity of the hydrogels, and that in the conditions of this study, the phosphate groups had an inhibitory effect on the deposition of CaP phases on HEMA-based hydrogels.

Experimental Calcification of HEMA-Based Hydrogels in the Presence of Albumin and a Comparison to the in Vivo Calcification

The precipitation patterns and characteristics of calcium phosphate (CaP) phases deposited on HEMA-based hydrogels upon incubation in simulated body fluid (SBF-2) containing a protein (human serum albumin) have been investigated in relation to the calcification in an organic-free medium (SBF-1) and to that occurring after subcutaneous implantation in rats. In SBF-2, the deposits occurred exclusively as a peripheral layer on the surface of the hydrogels and consisted mainly of "precipitated hydroxyapatite", a species deficient in calcium and hydroxyl ions, similarly to the deposits formed on the implanted hydrogels, where the deposited layer was thicker. In SBF-1, the deposits were mainly of brushite type. There was no evidence that albumin penetrated the interstices of hydrogels. As the X-ray diffraction patterns of the CaP deposits generated in SBF-2 showed a similar nature with those formed on the implanted hydrogel, it was concluded that the calcification in SBF-2 can mimic to a reliable extent the calcification process taking place in a biological environment.

Equivalences between refractive index and equilibrium water content of conventional and silicone hydrogel soft contact lenses from automated and manual refractometry

The purpose of the present study was to develop mathematical relationships that allow obtaining equilibrium water content and refractive index of conventional and silicone hydrogel soft contact lenses from refractive index measures obtained with automated refractometry or equilibrium water content measures derived from manual refractometry, respectively. Twelve HEMA-based hydrogels of different hydration and four siloxane-based polymers were assayed. A manual refractometer and a digital refractometer were used. Polynomial models obtained from the sucrose curves of equilibrium water content against refractive index and vice-versa were used either considering the whole range of sucrose concentrations (16-100% equilibrium water content) or a range confined to the equilibrium water content of current soft contact lenses (approximately 20-80% equilibrium water content). Values of equilibrium water content measured with the Atago N-2E and those derived from the refractive index measurement with CLR 12-70 by the applications of sucrose-based models displayed a strong linear correlation (r2 = 0.978). The same correlations were obtained when the models are applied to obtain refractive index values from the Atago N-2E and compared with those (values) given by the CLR 12-70 (r2 = 0.978). No significantly different results are obtained between models derived from the whole range of the sucrose solution or the model limited to the normal range of soft contact lens hydration. Present results will have implications for future experimental and clinical research regarding normal hydration and dehydration experiments with hydrogel polymers, and particularly in the field of contact lenses.

The effect of charged groups on protein interactions with poly(HEMA) hydrogels

Proteins, lipids and other biomolecules interact strongly with the acrylic-based biomaterials used for contact lenses. Although hydrogels are nominally resistant to protein fouling, many studies have reported considerable amounts of protein bound to poly(2-hydroxyethylmethacrylate) (PHEMA) lenses. This study examined the binding of a series of biomolecules (tear protein analogues, mucin and cholesterol) to poly(methylmethacrylate) (PMMA) and three HEMA-based hydrogels (PHEMA, HEMA plus methacrylic acid (P(HEMA–MAA)), HEMA plus methacrylic acid plus N-vinylpyrrolidone (P(HEMA–MAA–NVP))) by use of a quartz crystal microbalance with dissipation (QCM-D) monitoring. The QCM-D estimates changes in the mass and viscous constant for the adsorbed layer through measurements of frequency and dissipation. Protein interaction with each of the test materials caused a net increase in mass of the material indicating protein binding except for lysozyme interacting with P(HEMA–MAA). A net decrease in mass was observed for lysozyme interacting with P(HEMA–MAA) which may be ascribed to lysozyme collapsing the hydrogel by expelling water. A net mass decrease was observed for cholesterol interacting with each of the hydrogel materials, while a mass increase was observed on PMMA.

Changes to Tear Film Parameters During Wear of Hema-Based Hydrogel Lenses

Changes to Tear Film Parameters During Wear of Hema-Based Hydrogel Lenses

Quantitative evaluation of bacteria adherent to polyelectrolyte HEMA-based hydrogels.

The use of adhesive poly(HEMA)-based hydrogels is standard practice in dental restorative procedures. Microorganisms, which potentially can cause oral pathologies, may colonize these polymers. In the present work, bacterial adhesion to polymers prepared with 2-hydroxyethyl methacrylate (HEMA) and to different molar ratios of 2-acrylamido-2-methylpropane-sulfonic acid (AMPS) and/or to 2-methacryloyloxyethyl-tri-methyl-ammonium chloride (METAC) co-monomers were tested. A colorimetric assay system that utilizes the Microbo revelation medium (Microbo srl, Rome, Italy) for microbial counts is shown to be capable of counting the number of adherent bacterial cells without removing them from polymer surfaces. In conditions that mimic those present in the oral cavity, similar bacterial adhesion percentages on the same polymer were observed with the different bacteria belonging to both gram-positive and gram-negative genera, such as Streptococcus sobrinus and Streptococcus oralis (resident microorganisms in the oral cavity) and Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa (transient microorganisms in the oral cavity). It is determined that the physico-chemical characteristics of poly(HEMA)-based hydrogels are the major factors promoting bacterial adhesion, which increased with increasing water content in the swollen polymers, reaching maximal values on the cationic polymers.

Properties of PVA-AA cross-linked HEMA-based hydrogels

Poly(HEMA) hydrogel is usually prepared by using 1,1,1-trimethylol propane trimethacrylate and ethylene glycol dimethacrylate as the crosslinkers. Another method using PVA-AA (polyvinyl alcohol partially esterified with acryloyl chloride) as the cross linker is reported here. Two hydrogels, co-A1H9 and co-A2H8, were prepared by the polymerization of HEMA in the presence of 10% and 20% PVA-AA, respectively. The presence of PVA-AA reduced the water content from 32% to 25% in the resultant copolymer, whereas Tg did not change significantly. Co-A1H9 had an elastic modulus of 6.3 Mpa, which is much higher than 3.9 MPa and 3.7 MPa for poly(HEMA) and co-A2H8, respectively. The interfacial energies of poly(HEMA), co-A1H9 and co-A2H8 were calculated to be 0.52, 0.65 and 0.71 dyne/cm2, respectively, whereas the fractional polarities of these three hydrogels were all about 0.74. Thus a HEMA-based hydrogel with surface properties similar to poly(HEMA) but with stronger mechanical strength was successfully prepared. This copolymeric hydrogel could provide a choice other than the conventionally cross linked poly(HEMA) for various applications.