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Study of blood compatible polymers. III. Copolymers of N-benzyl, N-(2-hydroxyethyl) acrylamide and 2-hydroxyethyl methacrylate.

Copolymerization of 2-hydroxyethyl methacrylate (HEMA) and N-benzyl, N-(2-hydroxyethyl) acrylamide (BENAAm) was carried out at different mole ratios of the monomers to obtain copolymers of varying composition. BENAAm content of the copolymers varies between 13 and 70%. Investigation of the interaction of rabbit platelets with these polymer surfaces showed that copolymers with higher BENAAm content inhibit the platelet deformation. Human umbilical cord fibroblast cells proliferated very well on the copolymer surfaces. The cell growth rate on polyHEMA was relatively low. Maximum cell growth was observed on the copolymer having 87% HEMA.

Acrylic Resins↗

Radiopaque poly(2-hydroxyethyl methacrylate) particles containing silver iodide complexes tested on cell culture.

Silver iodide complexes have been used as an effective radiopacifying agent to prepare radiopaque poly(2-hydroxyethyl methacrylate) (poly(HEMA)) particles. Incorporation of silver iodide complexes inside the poly(HEMA) particles was achieved by first swelling particles in potassium iodide solution and precipitating the silver iodide complexes using a 30 wt% solution of silver nitrate. The dry particles contained 15 wt% of silver iodide complexes. Particles were easily monitored using a standard imaging technique based on X-ray absorption. Toxicity of the particles has been determined in in vitro experiments on a cell culture. As no inhibition of growth of cells surrounding the particles was observed, they can be considered non-toxic.

Biocompatible Materials↗

Immunofluorescence and enzyme histochemistry on consecutive sections from glycol-methacrylate-embedded bone marrow, lymph node and kidney specimens.

We describe an immunohistochemical technique adapted to tissues embedded in glycol-methacrylate (GMA). 1-micron-thick GMA sections from kidney, lymph node and bone marrow biopsies were trypsinized and then incubated with F(ab)2 antisera. GMA sections presented some distinct advantages with respect to compared paraffin and cryostatic sections: (1) reduction of background fluorescence, (2) higher resolution of morphologic details, (3) possibility of studying undecalcified bone marrow specimens and (4) possibility of coupling histochemistry with immunofluorescence on consecutive sections. Moreover, in a case of lymphoplasmacytoid lymphoma specific immunostaining for membrane IgM was obtained on GMA sections.

Acid Phosphatase↗

Continuous-flow bioluminescent determination of ATP in platelets using firefly luciferase immobilized on epoxy methacrylate.

Firefly luciferase was immobilized on epoxy methacrylate beads and used for a continuous-flow assay of ATP extracted from platelets. The immobilized luciferase had a half-life of 3 days at 25 degrees C; there was a 25% recovery of luciferase activity upon immobilization, and ca 50 reactors were made from 1 mg of commercial enzyme. The sensitivity of the assay was 0.3 pmol of ATP, and the response was linear between 1 and 500 pmol of ATP. The ATP content of platelets obtained with the present method correlated well with those obtained using soluble luciferase.

Adenosine Triphosphate↗

Influence of degree of crosslinking on 5-fluorouracil release from poly(2-hydroxyethyl methacrylate) hydrogels.

Controlled release of 5-fluorouracil (5-FU) from poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogels with three different degrees of crosslinking is reported. The swelling kinetic of PHEMA hydrogels in water was studied at different disc thicknesses and temperatures, and the diffusion coefficient and activation energy of the process were obtained. The gels were loaded with 5-FU by immersing them in concentrated aqueous solutions of the drug. The 5-FU release was studied as a function of temperature, disc thickness, disc load and degree of crosslinking of the gels; the diffusion coefficient and activation energy of the release process were also obtained.

Chemistry, Pharmaceutical↗

Phacoemulsification after retinal detachment surgery.

PURPOSE: To evaluate the outcomes of phacoemulsification in eyes that had previous retinal detachment (RD) surgery. SETTING: Hayashi Eye Hospital, Fukuoka, Japan. METHODS: Ninety-six eyes of 90 consecutive patients who had phacoemulsification after previous RD surgery (RD group) were included. Fifty-one fellow eyes that had not had RD surgery but did have phacoemulsification served as controls (control group). Recurrence of RD, visual acuity, complications, and the neodymium:YAG (Nd:YAG) laser capsulotomy rate were examined. RESULTS: Recurrent RD after phacoemulsification occurred in 2 eyes (2.1%) in the RD group. Three eyes (5.9%) in the control group developed RD postoperatively. The incidence of RD was not significantly different between the 2 groups (P =.3416). The mean final visual acuity in the RD group was 20/30, significantly worse than in the control group (P =.0099). Posterior capsule opacification developed in 29 eyes (30.2%) in the RD group and 11 eyes (21.6%) in the control group; the difference between the groups was not significant. Eighteen eyes (43.9%) that had implantation of a poly(methyl methacrylate) (PMMA) intraocular lens (IOL) and 7 eyes (6.6%) that received an acrylic IOL had an Nd:YAG capsulotomy; the capsulotomy rate was significantly higher in eyes with a PMMA IOL than in eyes with an acrylic IOL (P<.0001). CONCLUSIONS: The rate of recurrent RD after phacoemulsification in eyes that had previous RD surgery was similar to that of new occurrence of RD in fellow eyes without RD before phacoemulsification. Because the Nd:YAG capsulotomy rate was lower in eyes with acrylic IOLs than in eyes with PMMA IOLs, acrylic IOLs are recommended for eyes at high risk for RD.

Aged↗

Implantation of p(HEMA)-collagen composite into bone.

The replacement of bone defects is very important in clinical practice. This study compares biological properties of poly(2-hydroxyethyl methacrylate)-collagen composite with those exhibited by pure p(HEMA), an insoluble fraction of calf skin collagen (ISC-40) and demineralized bone matrix after implantation into pig or dog femurs. The levels of biodegradation or destruction of implants and healing of bone defects were studied using X-ray photography, histology and enzyme histochemistry. The results indicated a significant effect of collagen on biological destruction of the p(HEMA)-composite implants; even a minute amount of collagen influences this process dramatically. A stimulatory action of collagen on new bone formation may be of importance in bone defect healing.

Animals↗

Anticancer drug, ara-C, release from pHEMA hydrogels.

This study investigates the controlled release of cytarabine (ara-C), an anticancer drug, from a polymeric matrix of lightly cross-linked poly(2-hydroxyethyl methacrylate) (pHEMA). The swelling of pHEMA discs in water was analysed as a function of temperature and thickness of xerogel discs. The fractional swelling was linear in (time)1/2 for short time periods. Drug release kinetics were examined as a function of temperature, initial drug load and thickness of pHEMA discs. The fraction of available drug release was also linear in (time)1/2 during the initial stages. These studies allow for the determination of diffusion coefficients for both the transport of water into the hydrogel and ara-C release from the polymer.

Biocompatible Materials↗

An oral delivery device based on self-folding hydrogels.

A self-folding miniature device has been developed to provide enhanced mucoadhesion, drug protection, and targeted unidirectional delivery. The main part of the device is a finger like bilayered structure composed of two bonded layers. One is a pH-sensitive hydrogel based on crosslinked poly(methyacrylic acid) (PMAA) that swells significantly when in contact with body fluids, while the other is a non-swelling layer based on poly(hydroxyethyl methacrylate) (PHEMA). A mucoadhesive drug layer is attached on the bilayer. Thus, the self-folding device first attaches to the mucus and then curls into the mucus due to the different swelling of the bilayered structure, leading to enhanced mucoadhesion. The non-swelling PHEMA layer can also serve as a diffusion barrier, minimizing any drug leakage in the intestine. The resulting unidirectional release provides improved drug transport through the mucosal epithelium. The functionality of this device is successfully demonstrated in vitro using a porcine small intestine.

Adhesives↗

Adhesion of coagulase-negative staphylococci to methacrylate polymers and copolymers.

Adhesion of coagulase-negative staphylococci (CNS) was studied onto a homologous series of methacrylate polymers and copolymers. The materials varied in wettability (contact angles) and were either positively or negatively charged (zeta-potential). Bacterial adhesion experiments performed in a parallel-plate perfusion system showed that positively charged TMAEMA-Cl copolymers significantly promoted the adhesion of CNS as compared with all other methacrylate (co)polymers tested. The bacterial adhesion rates onto the positively charged surfaces are diffusion-controlled, whereas those onto the surfaces with a negative zeta-potential are more surface-reaction-controlled due to the presence of a potential energy barrier. The bacterial adhesion rates onto various poly (alkyl methacrylates) were similar. The number of adhering bacteria onto the negatively charged MMA/MAA copolymer did not differ from that onto pMMA, indicating that sufficient sites on the copolymer surface with the same potential energy barrier as that on pMMA, were available for adhesion. Decreasing rates of adhesion of CNS were observed onto MMA/HEMA copolymers with increasing HEMA content coinciding with increasing hydrophilicity. Low plateau values for the bacterial adhesion were observed on 50MMA/50HEMA, pHEMA, and 85HEMA/15MAA, indicating that the adhesion onto these materials was reversible. Four CNS strains with different surface characteristics all showed higher numbers of adhering bacteria onto 85MMA/15TMAEMA-Cl than onto 85MMA/15MAA and pMMA.

Binding Sites↗

Subcutaneous polymeric matrix system p(HEMA-BGA) for controlled release of an anticancer drug (5-fluorouracil). II: Release kinetics.

A subcutaneous polymeric drug delivery system, which consists of a polymeric matrix of poly(hydroxyethyl methacrylate-bisglycol acrylate), was developed. 5-fluorouracil was used as the model anticancer drug. Polymer-drug beads with a diameter of 3 mm were prepared by low-temperature radiation polymerization. In order to modify the release rate, polymeric beads with different composition, drug loading and crosslinking density were obtained. The kinetics of drug release were described by the expression Mt/M infinity = ktn. The diffusional release exponent 'n', which was calculated from the release curves, indicated that the mechanism of drug release from the polymeric matrix is due to the anomalous (non-Fickian) type of diffusion.

Acrylates↗

Effect of poly-HEMA hydrophilic gel environment on the photo-physical behavior of rhodamine dyes.

The absorption spectra of rhodamine B (RB) chloride, rhodamine 6G (R6G) tetrafluoroborate and rhodamine 6G chloride in poly-2-hydroxyethyl methacrylate hydrogel (PHEMA) matrix were studied using absorption spectroscopy in the visible region. The transport and aggregative properties of these ionic dyes in aqueous solution across the hydrophilic gel were also investigated. The similarities of absorption spectra of RB in aqueous solutions and in hydrogel host suggest that the hydrogel framework has a minor effect in their absorption spectra. In contrast, there is a relatively strong interaction or electrostatic forces between R6G dyes and the hydrogel matrix. The permeability of R6G chloride through hydrogel host is seen to be markedly higher than RB chloride and R6G tetrafluoroborate.

Chlorides↗

New radiopaque polyHEMA-based hydrogel particles.

New iodine-containing polymeric hydrogel particles were prepared by suspension radical copolymerization of 2-hydroxyethyl methacrylate (HEMA), 3-(methacryloylamidoacetamido)-2,4,6-triiodobenzoic acid (MABA) and ethylene dimethacrylate (EDMA) in an aqueous medium using azobisisobutyronitrile as an initiator and magnesium hydroxide as a suspension stabilizer. To impart porosity to the product, cyclohexanol and 1-dodecanol were added as inert diluents to the polymerization mixture. Particles containing 27 wt % iodine produced radiopacity sufficient to observe a clearly visible X-ray image. The equilibrium swelling behavior of the particles in water was characterized. Swelling of the particles dramatically increased by converting the acid groups of MABA into their Na+ form. The more MABA the copolymer particle contain, the higher is their swelling in the Na+ form.

Biocompatible Materials↗

A comparison of the effects of two hydroxyapatites and a methacrylate resin on bone formation in the rat ilium.

The bone response to two hydroxyapatite (HA) products (Osteogen and Alveograf) and a porous methacrylate resin material (HTR) in rats was compared. Fifty rats had four holes drilled in each iliac crest. The three alloplasts were placed in separate cavities and the fourth cavity was left empty as an absolute control. The survival times varied. The results were evaluated by subjective and histomorphometric analysis. Data were analyzed with ANOVA. There was a statistical difference in bone apposition between HTR and the HA products. The HTR was less osteoconductive, while HA consistently showed dense bone formation. The HA products are generally associated with greater bone formation, suggesting that HA is a better material for bone replacement than HTR.

Analysis of Variance↗

Drug release from acrylic polymers via channels and cracks: in vitro studies with hydrocortisone.

Release of hydrocortisone sodium succinate from acrylic resin was found to occur readily on elution in water at 37 degrees C. Increasing the degree of hydration of the acrylic resin by the addition of hydroxyethyl methacrylate impaired rather than enhanced the release of drug. The mechanism for the release of drug is believed to be surface release and drug dissolution into and diffusion via cracks and channels which are formed by incorporation of the drug, producing a 'drug-modified polymer'. Diffusion through the polymer matrix is believed to be insignificant. The results obtained are discussed in relation to this proposed model for drug release. A simple method for the manufacture of the core of an intra-oral insert capable of delivering drugs with MW greater than 400 for systemic and topical oral drug delivery is described.

Acrylic Resins↗

Bioreactor applications of glucose oxidase covalently bonded on pHEMA membranes.

Glucose oxidase was immobilized onto poly(2-hydroxyethyl methacrylate) membranes by covalent bonding through epichlorohydrin. The highest immobilization efficiency was found to be 17.4%. The Km values were 5.9 and 8.8 mM for free and bound enzymes, respectively, and the Vmax values were 0.071 and 0.067 mM/min for free and bound enzymes. When the medium was saturated with oxygen Km was not altered significantly but Vmax was. The optimum pHs for the free and bound enzyme were determined to be 5 and 6, respectively, and the optimum temperature was 30 degrees C for both forms. The inactivation constant for the bound enzyme was found to be 1.7 x 10(-4) min-1.

Enzymes, Immobilized↗

Evidence for Fickian water transport in initially glassy poly(2-hydroxyethyl methacrylate).

Water sorption which is not classically Fickian has been observed in a variety of polymers. Deviation from Fickian kinetics is widely assumed to be caused by rate-limiting polymer relaxation, despite minimal proof of this. To the contrary, the evidence accumulated in this work indicates that water transport in initially glassy poly(2-hydroxyethyl methacrylate) (PHEMA), an important water-swellable biomedical polymer, is controlled by Fickian diffusion. First of all, the fractional water uptake is initially linear and independent of sample thickness when plotted against the square root of time over initial thickness, as expected for a Fickian process. Furthermore, the moving solvent front also advanced with the square root of time. Temperature, polymer thermal history and initial solvent concentration all affected the sorption kinetics of PHEMA in manners consistent with a Fickian process. The invariably Fickian sorption mechanism is believed to be the consequence of the water molecule's small size and affinity for hydrophilic, swellable polymers.

Adsorption↗

Hydrogels in endovascular embolization. II. Clinical use of spherical particles.

In this study we report the results of clinical experiments, obtained with spherical particles made from poly(2-hydroxyethyl methacrylate) used in the embolization of arteriovenous anastomoses, in the suppression of pulmonary haemorrhage and haemoptysis and in the occlusion of some other arteries. So far we have used these particles in the treatment of 187 patients. It must be stressed that the advantage of spherical particles consists in the simplicity of their introduction into the blood vessel through a catheter, while in the blood vessel itself the particle swells in blood still more, when compared with the particle size in saline. This results in an immediate and permanent haemostatic effect. No revascularization occurs.

Embolization, Therapeutic↗