The efficacy of immediate implantation of macroporous poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel after laceration spinal cord injury in young rats / Eficacia de la implantación inmediata de hidrogel macroporoso de poli (N- [2-hidroxipropil] - metacrilamida) después de una lesión de la médula espinal en ratas jóvenes

SUMMARY: Spinal cord regeneration after mechanical injury is one of the most difficult biomedical problems. This article evaluates the effect of poly(N-[2-hydroxypropyl]-methacrylamide) hydrogel (PHPMA-hydrogel) on spinal cord regeneration in young rats after lateral spinal cord hemi-excision (laceration) at the level of segments T12-T13 (TrGel group). The locomotor function score (FS) and the paretic hindlimb spasticity score (SS) were assessed according to Basso-Beattie-Bresnahan (BBB) and Ashworth scales, respectively, and compared to a group of animals with no matrix implanted (Tr group). Regeneration of nerve fibers at the level of injury was evaluated at ~5 months after spinal cord injury (SCI). One week after the SCI induction, the FS on the BBB scale was 0.9±0.5 points in the Tr group and 3.6±1.2 points in the TrGel group. In the Tr group, the FS in 5 months was significantly lower than in 2 weeks after SCI, while no significant changes in FS were detected in the TrGel group over the entire observation period. The final FS was 0.8±0.3 points in the Tr group and 4.5±1.8 points in the TrGel group. No significant changes in SS have been observed in the TrGel group throughout the experiment, while the Tr group showed significant increases in SS at 2nd week, 6th week, 3th month and 5th month. The SS in 5 months was 3.6±0.3 points on the Ashworth scale in the Tr group and 1.8±0.7 points in the TrGel group. Throughout the observation period, significant differences in FS between groups were observed only in 5 weeks after SCI, whereas significant differences in SS were observed in 2, 3 and 6-8 weeks post-injury. Glial fibrous tissue containing newly formed nerve fibers, isolated or grouped in small clusters, that originated from the surrounding spinal cord matter have been found between the implanted hydrogel fragments. In conclusion, PHPMA-hydrogel improves recovery of the hindlimb locomotor function and promotes regenerative growth of nerve fibers. Further research is needed to clarify the mechanism of this PHPMA-hydrogel effect.

RESUMEN: La regeneración de la médula espinal después de una lesión mecánica es uno de los problemas biomédicos más difíciles. Este artículo evalúa el efecto del hidrogel de poli (N- [2-hidroxipropil] -metacrilamida) (PHPMA-hidrogel) sobre la regeneración de la médula espinal en ratas jóvenes después de la hemiescisión lateral de la médula espinal (lesión) a nivel de los segmentos T12 - T13 (Grupo TrGel). La puntuación de la función locomotora (FS) y la puntuación de espasticidad parética de las patas traseras (SS) se evaluaron de acuerdo con las escalas de Basso- Beattie-Bresnahan (BBB) y Ashworth, respectivamente, y se compararon con un grupo de animales sin matriz implantada (grupo Tr). Se evaluó la regeneración de las fibras nerviosas al nivel de la lesión ~ 5 meses después de la lesión de la médula espinal (LME). Una semana después de la inducción de SCI, el FS en la escala BBB fue 0,9 ± 0,5 puntos en el grupo Tr y 3,6 ± 1,2 puntos en el grupo TrGel. En el grupo Tr, el FS en 5 meses fue significativamente menor que en 2 semanas después de SCI, mientras que no se detectaron cambios significativos en FS en el grupo TrGel durante el período de observación. El FS final fue de 0,8 ± 0,3 puntos en el grupo Tr y de 4,5 ± 1,8 puntos en el grupo TrGel. No se han obser- vado cambios significativos en SS en el grupo TrGel durante el experimento, mientras que el grupo Tr mostró aumentos significativos en SS en la 2ª semana, 6ª semana, 3º mes y 5º mes. La SS en 5 meses fue de 3,6 ± 0,3 puntos en la escala de Ashworth en el grupo Tr y de 1,8 ± 0,7 puntos en el grupo TrGel. A lo largo del período de observación, se observaron diferencias significativas en FS entre los grupos solo en 5 semanas después de la LME, mientras que se observaron diferencias significativas en SS en 2, 3 y 6-8 semanas después de la lesión. Entre los fragmentos de hidrogel implantados se observó tejido fibroso glial que contenía fibras nerviosas recién formadas, aisladas o agrupadas en pequeños grupos, que se originaban a partir de la materia de la médula espinal circundante. En conclusión, PHPMA-hydrogel mejora la recuperación de la función locomotora de las patas traseras y promueve el crecimiento regenerativo de las fibras nerviosas. Se requieren más estudios para aclarar el mecanismo del efecto de hidrogel PHPMA.

Evaluation of Bone Regeneration on Polyhydroxyethyl-polymethyl Methacrylate Membrane in a Rabbit Calvarial Defect Model.

This study was conducted to evaluate the capacity of guiding bone regeneration of polyhydroxyethyl-polymethyl methacrylate (PHEMA-PMMA) membrane as a guided tissue regeneration membrane for bone defects. Two 8-mm diameter transosseous round defects were made at the parietal bone of 18 New Zealand White rabbits. Defects were covered with or without PHEMA-PMMA membrane. Radiological and histological evaluation revealed that the bone tissue over the defect was more regenerated with time in both groups. However, there was significantly more bone regeneration at 8 weeks in the experimental group than the control group (p<0.05). There was no sign of membrane degradation or tissue inflammation and no invasion of muscle and fibrous tissue into defects. PHEMA-PMMA is a potential material for guided tissue regeneration membrane as it induces no adverse tissue reaction and effectively supports selective bone regeneration.

Nanoengineered particles for enhanced intra-articular retention and delivery of proteins.

Localized intra-articular delivery of anti-inflammatory proteins can reduce inflammation in osteoarthritis but poses a challenge because of raid clearance within few hours of injection. A new class of polymer is developed that forms self-assembled nanoparticles ranging from 300 to 900 nm and demonstrates particle size dependent prolonged retention in intra-articular joint spaces compared to bolus protein over a period of 14 d.

Synthesis and characterization of curcumin loaded polymer/lipid based nanoparticles and evaluation of their antitumor effects on MCF-7 cells.

BACKGROUND: Hybrid materials are synthesized using hydrophilic polymer and lipids which ensure their long term systemic circulation through intravenous administration and enhance loading of hydrophobic drugs. The purpose of this study is to prepare, characterize and evaluate the in vitro efficacy of curcumin loaded poly-hydroxyethyl methacrylate/stearic acid nanoparticles in MCF-7. METHODS: C-PSA-NPs, prepared using the emulsification-solvent evaporation method were characterized by dynamic laser scattering, SEM, AFM, FT-IR, X-ray diffraction, and TGA. The in vitro release behavior was observed in PBS pH7.4, the anticancer potential was analyzed by MTT assay, cell cycle and apoptosis studies were performed through flow cytometry. C-PSA-NPs drug localization and cancer cell morphological changes were analyzed in MCF-7 cell line. RESULTS: C-PSA-NPs exhibited the mean particle size in the range of 184nm with no aggregation. The surface charge of the material was around -29.3mV. Thermal studies (TGA) and surface chemistry studies (FT-IR, XRD) showed the existence of drug curcumin in C-PSA-NPs. The MTT assay indicated higher anticancer properties and flow cytometry studies revealed that there were better apoptotic activity and maximum localization of C-PSA-NPs than curcumin. CONCLUSIONS: Polymer lipid based drug delivery appeared as one of the advancements in drug delivery systems. Through the present study, a novel polymer lipid based nanocarrier delivery system loaded with curcumin was demonstrated as an effective and potential alternative method for tumor treatment in MCF-7 cell line. GENERAL SIGNIFICANCE: C-PSA-NPs exhibited potent anticancer activity in MCF-7 cell line and it indicates that C-PSA-NPs are a suitable carrier for curcumin.

A nonviral pHEMA+chitosan nanosphere-mediated high-efficiency gene delivery system.

The transport of DNA into eukaryotic cells is minimal because of the cell membrane barrier, and this limits the application of DNA vaccines, gene silencing, and gene therapy. Several available transfection reagents and techniques have been used to circumvent this problem. Alternatively, nonviral nanoscale vectors have been shown to bypass the eukaryotic cell membrane. In the present work, we developed a unique nanomaterial, pHEMA+chitosan nanospheres (PCNSs), which consisted of poly(2-hydroxyethyl methacrylate) nanospheres surrounded by a chitosan cationic shell, and we used this for encapsulation of a respiratory syncytial virus (RSV)-F gene construct (a model for a DNA vaccine). The new nanomaterial was capable of transfecting various eukaryotic cell lines without the use of a commercial transfection reagent. Using transmission electron microscopy, (TEM), fluorescence activated cell sorting (FACS), and immunofluorescence, we clearly demonstrated that the positively charged PCNSs were able to bind to the negatively charged cell membrane and were taken up by endocytosis, in Cos-7 cells. Using quantitative polymerase chain reaction (qPCR), we also evaluated the efficiency of transfection achieved with PCNSs and without the use of a liposomal-based transfection mediator, in Cos-7, HEp-2, and Vero cells. To assess the transfection efficiency of the PCNSs in vivo, these novel nanomaterials containing RSV-F gene were injected intramuscularly into BALB/c mice, resulting in high copy number of the transgene. In this study, we report, for the first time, the application of the PCNSs as a nanovehicle for gene delivery in vitro and in vivo.

PHEA-graft-polymethacrylate supramolecular aggregates for protein oral delivery.

Salmon calcitonin (sCT) is characterized by a poor oral availability. A new copolymer, ß-poly(N-2-hydroxyethyl)-graft-{N-2-ethylene[2-poly(methacrylic acid sodium salt)isobutyrate]}-d,l-aspartamide (PHEA-IB-p(MANa(+))), was designed for the oral administration of sCT through the formation of supramolecular aggregates (SAs) based on electrostatic interactions. Several sCT/PHEA-IB-p(MANa(+)) weight ratios were characterized by turbidimetry, DLS, zeta potential, and microscopy analysis. After the incubation of sCT/PHEA-IB-p(MANa(+)) complex with digestive enzymes, 10% (w/w) of loaded sCT was released in the native form. In vitro investigation was carried out to determine the copolymer effect on the permeability of sCT in Caco-2 cell monolayers. sCT pharmacokinetic profile and the pharmacodynamic effect on calcium plasma level were determined following an oral administration of the lead sCT/PHEA-IB-p(MANa(+)) SA (1/5 ratio) in rats. The SA yielded a marked prolongation of the sCT lowering calcium effect. The maximum decrease, 35% with respect the basal calcium plasma level at time 0 h, was achieved after 4h post-administration, and after 7 h, a decrease of 20% was still present. Differently, sCT yielded a transient calcium decrease that was completely restored after 5h. The higher bioavailability of sCT administered as SA was confirmed by the pharmacokinetic studies. In fact, the AUC and the Cmax were about 15 times higher for the sCT formulated as SA than the free sCT. This study indicates the potentials of PHEA-IB-p(MANa(+)) as carrier of sCT for oral delivery.

Risk of severe adverse reactions to an injectable filler based on a fixed combination of hydroxyethylmethacrylate and ethylmethacrylate with hyaluronic acid.

BACKGROUND: Hydroxyethylmethacrylate and ethylmethacrylate in a fixed combination with hyaluronic acid has been used as an injectable filler for nearly a decade. Severe adverse reactions have been associated with this filler. OBJECTIVE: To characterize the adverse reactions to this filler. METHODS: Data from the Berlin registry for adverse reactions to injectable fillers were analyzed. The registry is a partially population-based registry with the aim of collecting adverse reactions to injectable fillers. Patients were interviewed based on a standardized questionnaire. RESULTS: Thirty-four of 118 (28.8%) registered patients were treated with this filler. Of 95 treated areas, 87 responded with a reaction (91.6%). The most frequently observed adverse events were the development of nodules (n=85) in 87 affected areas, discoloration (n=39), erythema or inflammation (n=32), and swelling (n=24). Most nodular reactions were rated as severe. The mean time after the last treatment until appearance of an adverse reaction was 23.1+/-22.8 months. CONCLUSION: Adverse reactions to this methacrylate filler are common. The mean latency period for these mostly severe rated reactions was nearly 2 years. Based on the frequency and severity of these reactions, the use of this filler does not seem to be advisable.

Pentablock copolymers of poly(ethylene glycol), poly((2-dimethyl amino)ethyl methacrylate) and poly(2-hydroxyethyl methacrylate) from consecutive atom transfer radical polymerizations for non-viral gene delivery.

Well-defined pentablock copolymers (PBPs) of P(HEMA)-b-P(DMAEMA)-b-PEG-b-P(DMAEMA)-b-P(HEMA) (in which PEG=poly(ethylene glycol), P(DMAEMA)=poly((2-dimethyl amino)ethyl methacrylate), and P(HEMA)=poly(2-hydroxyethyl methacrylate)), with different block lengths of P(DMAEMA), for non-viral gene delivery were prepared via consecutive atom transfer radical polymerizations (ATRPs) from the same di-2-bromoisobutyryl-terminated PEG (Br-PEG-Br) center block. The PBPs demonstrate good ability to condense plasmid DNA (pDNA) into 100-160 nm size nanoparticles with positive zeta potentials of 25-35 mV at PBPs/pDNA weight ratios of 5-25. The PBPs exhibit very low in vitro cytotoxicity and excellent gene transfection efficiency in HEK293 and COS7 cells. In particular, the transfection efficiencies of all the PBPs in HEK293 cells are comparable to, or higher than those of polyethylenimine (PEI, 25 kDa) at most weight ratios. The ability of the copolymers to condense plasmid DNA and the transfection efficiency of the resulting complexes are dependent on the chain length of P(DMAEMA) blocks. In addition to reducing the cytotoxicity and increasing the stability of the plasmid complexes, the PEG center block and the short P(HEMA) end blocks also help to enhance the gene transfection efficiency. Thus, the approach to well-defined block copolymers via ATRP provides a versatile means for tailoring the structure of non-viral gene vectors to meet the requirements of low cytotoxicity, good stability and high transfection capability for gene therapy applications.

Dexamethasone transport and ocular delivery from poly(hydroxyethyl methacrylate) gels.

We explore ocular delivery of dexamethasone (DX) via poly(hydroxyethyl methacrylate) (PHEMA) contact lenses, which are known to have a much higher bioavailability in comparison to eye drops. Three derivatives of dexamethasone (dexamethasone 21-disodium phosphate (DXP), dexamethasone, and dexamethasone 21-acetate (DXA)) are explored. These drugs are loaded in the gels by soaking in aqueous or ethanol solutions, and also by direct addition of the drug to the polymerizing mixture. Dynamic drug concentrations in the aqueous phase are monitored both in loading and release experiments. The data is utilized to determine the partition coefficients and the mean diffusivity, which includes contributions from both bulk and surface diffusion. Finally we utilize the transport model to predict the bioavailability of the three forms of dexamethasone for drug delivery via contact lenses. The transport of each of the drug is diffusion limited with diffusivities of 1.08 x 10(-11) and 1.16 x 10(-11) m(2)/s for DX and DXA, respectively. The diffusivities of DXP depend on concentration and on ionic strength, and are much smaller than those for DX and DXP. The bioavailability for delivery of these drugs via contact lenses is much higher than that for drops, and the bioavailability is the highest for DXA.

Intracellular delivery enhancement of poly(amino acid) drug carriers by oligoarginine conjugation.

Poly(2-hydroxytethyl aspartamide) (PHEA) was effectively translocated in both fixed and unfixed HeLa cells, when oligoarginine (Arg(8)) known as one of the cell-penetrating peptides was conjugated via a thioether linkage. The internalization of PHEA-Arg(8) into cells was a temperature-dependent process, and the studies at endocytosis inhibition conditions suggested that an endocytosis was a key mechanism. The fluorescence spectra of PHEA-Arg(8) in liposome solutions showed that PHEA-Arg(8) was collectively adsorbed in the negative liposome membrane due to the high cationic property of a conjugated Arg(8), representing that a surface adsorption was a first step in the internalization of PHEA-Arg(8). The membrane leakage activity of PHEA-Arg(8) was much lower than that of Arg(8) own, meaning that PHEA-Arg(8) does not effectively disrupt the cell membrane integrity. The uptake of polymer conjugates increased with the incubation time and reached saturation after several hours. The increase in the number of peptide conjugated to one polymer chain could increase the collective adsorption of polymer conjugates and enhance the cellular uptake. Thus, it is believed that PHEA-Arg(8) could be internalized by an adsorptive-endocytosis. A model conjugate of PHEA-Arg(8) with methotrexate (PHEA-MTX-Arg(8)) inhibited the cell proliferation about several orders of magnitude more active than PHEA-MTX.

[Cosmetic soft-tissue augmentation treatment]. / Behandling med kosmetiske bløddelsfyldere.

An increasing number of patients undergo soft-tissue augmentation. The quality depends on the applied filler substance, the compliance of the patient and the physician. Long-term adverse reactions are referred to as nodules or granulomas. Nodules following degradable gels and polyacrylamide hydrogel are always caused by bacteria. Nodules following inert, hydrophobic silicone gel and combination gels may emerge years after the injection. They are often caused by a low-grade infection with ensuing enhanced fibrosis and treatment requires a specialist.

Improving the loading and release of NSAIDs from pHEMA hydrogels by copolymerization with functionalized monomers.

Poly(hydroxyethyl methacrylate), pHEMA, hydrogels are widely used for preparing implants, contact lenses, and other biomedical devices, which in many circumstances should load drugs to deliver them in the adjacent tissues. To enhance the potential of pHEMA hydrogels as nonsteroidal anti-inflammatory drugs (NSAIDs) delivery systems, 4-vinyl-pyridine (VP) and N-(3-aminopropyl) methacrylamide (APMA) were incorporated to the network (25-150 mM). The incorporated monomers did not change the viscoelastic properties neither the state of water, but remarkably increased the amount of ibuprofen (up to 10-fold) and diclofenac (up to 20-fold) loaded. Dried loaded pHEMA-APMA and pHEMA-VP hydrogels quickly swelled in water but ionic/hydrophobic interactions prevented the amount of drug released to be above 10%. By contrast, once the water-swollen hydrogels were transferred to pH 5.8 or 8.0 phosphate buffers or NaCl solutions, the release was prompted by competition with ions of the medium. The remaining of hydrophobic interactions and the high polymeric density of the pHEMA hydrogels contributed to sustain the release process for at least 24 h for ibuprofen and almost 1 week for diclofenac. The release rate was independent of the salt content and pH in the physiological range of values, which enables the design of hydrogel-based delivery systems with predictable release rate.

An active wound dressing for controlled convective mass transfer with the wound bed.

Conventional wound dressings-gauze, plastic films, foams, and gels-do not allow for spatial and temporal control of the soluble chemistry within the wound bed, and are thus limited to a passive role in wound healing. Here, we present an active wound dressing (AWD) designed to control convective mass transfer with the wound bed; this mass transfer provides a means to tailor and monitor the chemical state of a wound and, potentially, to aid the healing process. We form this AWD as a bilayer of porous poly(hydroxyethyl methacrylate) (pHEMA) and silicone; the pHEMA acts as the interface with the wound bed, and a layer of silicone provides a vapor barrier and a support for connecting to external reservoirs and pumps. We measure the convective permeability of the pHEMA sponge, and use this value to design a device with a spatially uniform flow profile. We quantify the global coefficient of mass transfer of the AWD on a dissolvable synthetic surface, and compare it to existing theories of mass transfer in porous media. We also operate the AWD on model wound beds made of calcium alginate gel to demonstrate extraction and delivery of low molecular weight solutes and a model protein. Using this system, we demonstrate both uniform mass transfer over the entire wound bed and patterned mass transfer in three spatially distinct regions. Finally, we discuss opportunities and challenges for the clinical application of this design of an AWD.

La evolución de la adhesion a dentina / The history in dentinal adhesion

Se realiza una revisión a la historia de la adhesión comenzando en las culturas precolombinas ("era pre-adhesiva"), para continuar en la "era adhesiva" con las aportaciones de Buonocuore y la aparición del Bis-GMA, pasando por la incorporación al mercado dental de los fosfatos, los oxalatos, el sistema Gluma. Se analiza también la descripción de la capa híbrida por Nakabayashi, después aparecen los primeros acuosos y la hibridación de tejidos duros hasta llegar a los sistemas adhesivos autograbadores (AU)

An overview of dentin bonding history is done by the author since early south American cultures (pre-adhesive age) to continued in the adhesive age with Buonoccore's findings and the rise of Bis-GMA and the first dentin adhesives based on phosphate, oxalate and Gluma system. Nakabayashi's hybrid layer is described and the evolution of aqueous primers and hard tissues hybridation until arrival of newest self-etching adhesives (AU)

Combined stent implantation and embolization with liquid 2-polyhydroxyethyl methacrylate for treatment of experimental canine wide-necked aneurysms.

The purpose of the study was the evaluation of 2-polyhydroxyethyl methacrylate (2-P-HEMA) for endovascular liquid embolization of experimental side-wall aneurysms following stent protection in a canine model. The swelling behaviour and polymerization characteristics of 2-P-HEMA in different solutions were investigated in vitro. Different methods for applications were tested in a latex aneurysm model under pulsatile flow conditions. Twenty broad-based carotid side-wall aneurysms were microsurgically produced in five dogs. Four weeks after surgery self-expandable nitinol stents were placed, covering the orifice of the aneurysms. 2-P-HEMA was injected via a microcatheter, which was positioned through the meshwork of the stent. Control angiography was performed immediately after treatment and after 1, 6 and 9 months. In-vivo stent placement succeeded in all but one case. Two aneurysms occluded spontaneously after stent placement. Combined embolization of 17 aneurysms using a stent and 2-P-HEMA was performed. Eleven aneurysms could be primarily completely occluded (65%). A small remaining neck was evident in six aneurysms. Efflux of 2-P-HEMA during the process of embolization was observed in seven aneurysms, due to an excess volume of 2-P-HEMA. The excessive 2-P-HEMA led to significant vessel stenosis in two cases. Two carotid arteries (three treated aneurysms) occluded after 1 month, due to insufficient anticoagulation management. Histological examination of embolized aneurysms revealed no foreign-body or inflammatory reaction. A smooth neo-intimal layer covered the stented vessel segment. Liquid embolization of side-wall aneurysms with 2-P-HEMA is technically feasible. Embolotherapy of aneurysms with liquid agents still has the risk that embolic material will exit even when it is stent-protected. To avoid this problem, stents with smaller strut diameter and/or additional balloon-protection are required. The inert 2-P-HEMA seems to be a promising agent for combining techniques of aneurysm treatment.

Transarterial embolization with HEMA-MMA of variant convexity-superior sagittal sinus dural arteriovenous fistula--case report.

A 62-year-old male presented with a variant dural arteriovenous fistula (DAVF) within the wall of the convexity-superior sagittal sinus, fed by branches of the bilateral external carotid arteries and only cortical venous drainage despite the presence of a patent sinus. Transarterial embolization with poly(2-hydroxyethyl methacrylate-co-methyl methacrylate) (HEMA-MMA) was performed, resulting in complete obliteration of the DAVF. Embolization with HEMA-MMA is an effective and safe procedure for the treatment of DAVF.

Experimental corneal neovascularization by basic fibroblast growth factor incorporated into gelatin hydrogel.

The study was designed to investigate the feasibility of using an acidic gelatin hydrogel as a biodegradable vehicle for basic fibroblast growth factor (bFGF). bFGF was incorporated by polyion complexation into a biodegradable hydrogel prepared by cross-linking acidic gelatin with the isoelectric point of 4.9. The dried hydrogel (sized to 2x1 mm) was hydrated with bFGF aqueous solution including different doses of bFGF (20, 50, 125, 250 and 500 ng) and implanted into a rabbit corneal pocket (2.5x2 mm). As a control group, the gelatin hydrogel without bFGF or bFGF alone (500 ng) was used. Corneal angiogenesis was evaluated by biomicroscopy, corneal fluorescein angiography and histology for 21 days. Photographs were taken and corneal angiogenesis was evaluated by image analysis. The hydrogel degraded with time after its implantation into the corneal pocket. Experimental eyes receiving the hydrogel containing more than 50 ng of bFGF demonstrated significant corneal angiogenesis. Control eyes and eyes receiving the hydrogel containing 20 ng of bFGF showed no corneal angiogenesis. Corneal angiogenesis, which occurred on the 3rd or 4th day after implantation, reached maximal growth on about day 7 and regressed from day 10 after implantation. The area of angiogenesis showed a dose-dependency on bFGF. The gelatin hydrogel itself induced neither angiogenesis nor inflammation. These results suggested that acidic gelatin hydrogel releases bioactive bFGF with its biodegradation, resulting in corneal neovascularization.

Evaluation of poly(2-hydroxyethyl methacrylate) gels as drug delivery systems at different pH values.

Studies of dynamic and equilibrium swelling, structural characterisation and solute transport in swollen poly(2-hydroxyethyl methacrylate) gels (pHEMA) cross-linked with tripropyleneglycol diacrylate (TPGDA) were done for a wide range of TPGDA concentrations. The influence of the pH on these pHEMA properties was evaluated. In swelling studies it was found that in changing the pH from 6.5 to 12.0, a large increase in swelling occurred, from approximately 48 to 55%, for the lowest concentration of TPGDA (1 mol%), and from 40 to 80% for the highest concentration (10 mol%). Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC) measurements were made after the equilibrium swelling of the gels at different pH values, to explain these results. The advantage of using these gels as controlled drug delivery systems is illustrated using salicylic acid (SA) as a model drug. The loading and the release of the SA were made at different pH values and the results obtained showed that it is possible to modulate the hydrogel performance by controlling an external factor, the pH at which the drug loading and release were performed.

[A biocompatibility study and the effects of slow-release antibiotic materials in the treatment of periodontal disease. II. The biocompatibility and behavior of polyhydroxyethyl methacrylate (pHEMA) as a slow-release material for tetracycline of metronidazole. A study of 2 cases]. / Studio sulla biocompatibilità e gli effetti di alcuni materiali a lento rilascio di antibiotico nel trattamento della malattia parodontale. Nota II. Biocompatibilità e comportamento del poliidrossietilmetacrilato (pHEMA) come materiale a lento rilascio di tetraciclina o di metronidazolo. Studio su due casi.

The study analyses the possibility of using polyhydroxyethyl methacrylate as a material for the slow release of antibiotic in periodontal pockets. The antibiotics examined were tetracycline and metronidazole. The aim of the study was to evaluate the biocompatibility of the material with periodontal tissue and the efficacy of the 2 prepared systems. Two sites were selected in 2 periodontopathic patients who after non-surgical treatment presented pockets measuring 8 and 7 mm. A sheet of pHEMA containing tetracycline was inserted in one and in the other a sheet containing metronidazole: both were left for 8 days in the chosen pockets. At the start and end of treatment PD and GI clinical indices were measured and the DMDx microbiological test was performed to identify Aa of Pg and Pi. The tissue reaction to pHEMA was evaluated using SEM analysis of two samples collected after 8 days of treatment. The microscopic results showed the optimal biocompatibility of both samples. Differences were noted with regard to clinical and microbiological efficacy. It was observed that the sheet of pHEMA containing tetracycline resulted in the disappearance of bleeding and a reduced depth of survey. Moreover, microbiological results showed a significant reduction in Porphyromonas gingivalis. The sheet of pHEMA containing metronidazole showed a lower level of therapeutic efficacy. Although reduced depth was noted, gingival bleeding was persistent and the reduction of bacteria analysed was not significant. In conclusion, the authors confirm the optimal biocompatibility of the material and its easy application, although further research, especially for pHEMA with metronidazole, must be carried out to improve drug kinetics, trying to maintain an effective local concentration throughout treatment.

Slow releasing of ara-C from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2-pyrrolidone) hydrogels implanted subcutaneously in the back of rats.

The release of cytarabine (ara-C) from poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate-co-N-vinyl-2pyrrolidone) hydrogels cross-linked with different amounts of ethyleneglycol dimethacrylate (EGDMA) 'in vivo' has been studied. Two ara-C loaded hydrogel discs, each with 25 mg of the drug, were subcutaneously implanted in the back of male Wistar rats. Total ara-C dose was 230 mg kg(-1). Ara-C and ara-U plasmatic concentration were determined by HPLC. Periods of constant drug concentration are observed from all gels. Ara-C concentrations in the steady-state are between 19.0 +/- 2.0 and 2.2 +/- 0.8 micromol l(-1). The release time of ara-C was between 3 days from pH EMA 0.5% and 16 days from H80/VP20/E15 gels. These results are very different of that obtained when ara-C is administered by intraperitoneal injection, in this case peaks of maximum concentration (between 24 +/- 1 and 3.9 +/- 0.4 microg ml(-1)) 30 min after the injection are originated, and no drug is detected 4 h after the injection.