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Studies on biodegradation and release of gentamicin sulphate from interpenetrating network hydrogels based on poly(acrylic acid) and gelatin: in vitro and in vivo.

Interpenetrating network hydrogels (IPNs) based on poly(acrylic acid) and gelatin (Ge) were evaluated for in vitro and in vivo biodegradation and in vivo release of gentamicin sulphate. In vitro and in vivo degradation studies demonstrated that with the increase of acrylic acid content in the polymer, the rate of degradation decreases, and a reverse phenomenon was observed with increasing Ge content in the hydrogel. The rate of in vivo degradation was much lower than in vitro degradation. Incorporation of gentamicin sulphate in hydrogel further reduces their degradation. In vitro and in vivo drug release profile showed a burst effect, followed by controlled release. Drug concentration was measured in the local skin tissue, blood serum, kidney, liver and spleen. The local skin tissue concentration of 50% and 100% gentamicin sulphate, loaded full IPNs (i.e., Ax-1 and Ax-2), was found to be higher (20+/-2mug/g) than the minimum bactericidal concentration for Staphylococcus aureus (1.2mug/g) and Pseudomonas aeruginosa (10mug/g), respectively, for a study time of 60 days.

Acrylic Resins↗

Chitosan-poly(acrylic) acid polyionic complex: in vivo study to demonstrate prolonged gastric retention.

The aim of this study was to develop a chitosan-poly(acrylic) acid based controlled drug release system for gastric antibiotic delivery. Different mixtures of amoxicillin (A), chitosan (CS), and poly(acrylic) acid (PAA) were employed to obtain these polyionic complexes. A non-invasive method was employed for determining the gastric residence time of the formulations. It was studied the swelling behavior and drug release from these complexes. Gastric emptying rate study was performed by means of the [13C]octanoic acid breath test. The gastric emptying rates of two different formulations (conventional and gastric retentive system) were studied. Swelling studies indicated that the extent of swelling was greater in the polyionic complexes than in the single chitosan formulations. The amoxicillin diffusion from the hydrogels was controlled by the polymer/drug interaction. The property of these complexes to control the solute diffusion depends on the network mesh size, which is a significant factor in the overall behavior of the hydrogels. The gastric half-emptying time of the polyionic complex was significantly delayed compared to the reference formulation, showing mean values of 164.32+/-26.72 and 65.06+/-11.50min, respectively (P<0.01). The results of this study suggest that, these polyionic complexes are good systems for specific gastric drug delivery.

Acrylic Resins↗

Macroporous poly(sucrose acrylate) hydrogel for controlled release of macromolecules.

We have studied the controlled release of proteins from poly(sucrose acrylate) hydrogels. The hydrogels were prepared by a two-step procedure in which sucrose was first acylated to sucrose-1'-acrylate followed by free radical polymerization. By adjusting the cross-link ratio and initial monomer concentration, the swelling ratio of the hydrogel was varied from five to 28. The mechanical strength of these hydrogels was comparable to that of the hydrogels with approximately the same swelling ratio. Scanning electron micrographs and mesh size calculations indicate that the hydrogel is macroporous, suggesting it may be suitable for a variety of biomedical applications. The release kinetics of beta-lactoglobulin, bovine serum albumin and gamma-globulin were studied as a function of initial monomer concentrations for the sucrose-based hydrogel. All of the release profiles were characterized by an initial burst of protein in the first 25 h followed by a long period of sustained release (> 500 h). The magnitude of the initial burst was reduced by increasing the initial monomer concentration and by increasing the molecular weight of the protein. A quantitative model based on the heterogeneous nature of hydrogel was developed to explain the observed release kinetics.

Acrylic Resins↗

Soft acrylic resin materials containing a polymerisable plasticiser I: mechanical properties.

Conventional soft acrylic resin materials depend on the use of plasticisers for their compliance. In aqueous environments the plasticisers leach out causing the material to harden. Use of a polymerisable plasticiser has been shown to solve this problem. One such material was developed but failed mechanically during clinical trial. The aim of this study was to reformulate to produce a material with improved strength. Three different methacrylate monomers were used with two different levels of plasticiser, each monomer mix was used with the same copolymer powder at three powder/liquid ratios. Tensile strength, tear energy and hardness were measured and results compared with 'Supersoft', a proprietary plasticised acrylic resin soft lining material. All the experimental materials had a higher tensile strength than the original Parker/Braden material. The 30% plasticiser materials with the higher powder/liquid level had strength, tear energy and hardness values in the same range as 'Supersoft'. Materials of improved strength have been produced.

Acrylic Resins↗

Plasma copolymer surfaces of acrylic acid/1,7 octadiene: surface characterisation and the attachment of ROS 17/2.8 osteoblast-like cells.

The purpose of this study was: (a) to examine the effect of plasma-gas composition on plasma polymer oxygen/carbon (O/C) ratio, functional group composition and stability in water, and then (b) to examine cell attachment to surfaces containing different concentrations of O/C and functional groups. Oxygen-functionalised surfaces were deposited by means of the plasma copolymerisation of acrylic acid/1,7-octadiene. The use of a diluent hydrocarbon allowed the deposition of surfaces with a range of O/C concentrations. Plasma copolymer surfaces were characterised by X-ray photoelectron spectroscopy (XPS). Changes in functional group composition with % acrylic acid monomer and the non-dispersive and dispersive parts of the surface energy of these plasma copolymers were measured. The solubility of the plasma copolymers was assessed by means of XPS. The degree of attachment of ROS 17/2.8 osteoblast-like cells to plasma copolymer surfaces deemed to be 'stable' in aqueous medium was measured. Tissue culture polystyrene (TCPS) was included as a control. Attachment was found to be greatest to the plasma copolymer surface with an O/C of 0.11. This surface had a carboxylic acid concentration of ca. 3%. Attachment did not correlate with increased surface wettability (i.e. the non-dispersive component of the surface energy).

Acrylates↗

Soft acrylic resin materials containing a polymerisable plasticiser II: water absorption characteristics.

The main disadvantage of soft acrylic resin denture lining materials is the loss of plasticiser leading to gradual hardening. One possible solution to this problem is the use of a polymerisable plasticiser. A material based on such a plasticiser failed in clinical trials due to a combination of prolonged water uptake and low strength. Similar materials with improved strength have been developed and it is the aim of this study to investigate their water uptake characteristics. Water uptake from distilled water, an artificial saliva and 0.9 M saline has been determined for three experimental materials and 'Supersoft', a commercial plasticised acrylic resin denture lining material. Solubilities were determined after 6 months and diffusion coefficients calculated where appropriate. All the experimental materials had a lower uptake and solubility than 'Supersoft' in all solutions. For each material uptake was lower from solution than from distilled water. All diffusion coefficients were in the range expected for this type of material. The water uptake of the experimental materials was influenced by the relative hydrophilicity of the monomer used.

Absorption↗

Hydrophilic acrylic intraocular lens optic and haptics opacification in a diabetic patient: bilateral case report and clinicopathologic correlation.

OBJECTIVE: To report clinicopathologic and ultrastructural features of two opacified single-piece hydrophilic acrylic intraocular lenses (IOLs) explanted from a diabetic patient. DESIGN: Interventional case report with clinicopathologic correlation. SETTING: A 64-year-old white female underwent phacoemulsification and implantation of a single-piece hydrophilic acrylic lens (SC60B-OUV; Medical Developmental Research, Inc., Clear Water, FL) in October 1998 in the left eye and in July 1999 in the right eye. The best-corrected visual acuity after surgery was 20/60 in the left eye and 20/50 in the right eye. The patient had a marked decrease in visual acuity in June 2000 as a result of a milky, white opalescence of both lenses. Intraocular lens explantation and exchange was performed in both eyes and the explanted IOLs were submitted to our center for detailed pathologic, histochemical, and ultrastructural evaluation. They were stained with alizarin red and the von Kossa method for calcium, and also underwent scanning electron microscopy and energy dispersive radiograph spectroscopy to ascertain the nature of the deposits leading to opacification. MAIN OUTCOME MEASURES: Documentation of calcium deposits confirmed by histochemical stains and surface analyses. RESULTS: Opacification of the IOL was found to be the cause of decreased visual acuity. The opacification involved both the IOL optic and the haptics in the left eye and was confined to the IOL optic in the right eye. Histochemical and ultrastructural analyses revealed that the opacity was caused by deposition of calcium and phosphate within the lens optic and haptics. CONCLUSIONS: There are two features that distinguish this case from those reported earlier. This is the first clinicopathologic report of lens opacification that has involved completely the lens optic and the haptics. Second, these two explanted IOLs document the first bilateral case. This process of intraoptic and haptic opacification represents dystrophic calcification of unknown cause. Diabetic patients appear to be more severely and more often affected by lens opacification. Long-term follow-up of diabetic patients implanted with this IOL design should be maintained by surgeons and manufacturers.

Acrylic Resins↗

Recyclable characteristics of hyaluronate-polyhydroxyethyl acrylate blend hydrogel for controlled releases.

Hyaluronate-hydroxyethyl acrylate blend hydrogels which have a wide range of composition and characteristics were investigated. Glycidyl methacrylate derivatized hyaluronate (GMA-HA) were synthesized by coupling GMA to hyaluronate (HA) in the presence of a photoinduced initiator for polymerization. By copolymerizing radically GMA-HA and hydroxyethyl acrylate (HEA) under various compositions (weight ratios of HEA and GMA-HA: 1-20), GMA-HA hydrogels could be prepared in wide ranges of characteristics. These HA-PHEA gels possessed the feature that the dried ones recovered completely to the original swelling states on repeated runs, i.e. recyclable gels. The water contents of these hydrogels in equilibrium swellings in water (W(w)) were 0.99-0.86, and their viscoelastic properties were measured by a creep. The spontaneous elastic moduli were 1.05x10(5)-1.94x10(5) N m(-2), and they were mechanically tough. Their effective charge densities were estimated from the partition coefficients of sodium benzoate (NaBA) and decreased from -0.033 to -0.044 mol dm(-3) with increasing contents of HEA. Release of NaBA was studied, and the diffusion coefficients were found to be from 6.95x10(-10) to 0.12x10(-10) m(2) s(-1) with increasing the ratio of HEA. Their diffusion coefficients were found to be much less than the values estimated from the lattice model.

Acrylates↗

Mucoadhesive drug carrier based on interpolymer complex of poly(vinyl pyrrolidone) and poly(acrylic acid) prepared by template polymerization.

To develop a new mucoadhesive drug carrier, poly(vinyl pyrrolidone) (PVP)/poly(acrylic acid) (PAA) interpolymer complexes were prepared by the template polymerization of acrylic acid using PVP as a template polymer. Fourier transform infrared results showed that the interpolymer complexes were formed by hydrogen bonds between the carboxyl groups of PAA and the carbonyl groups of PVP. The adhesive forces of the PVP/PAA interpolymer complexes were higher than that of commercial Carbopol 971. Moreover, the adhesive force and the release rate can be controlled by changing the mole ratios of PVP and PAA. The release rates of ketoprofen from the PVP/PAA interpolymer complexes showed pH-dependency, and were slower at lower pH. The release rate of ketoprofen from the complex seemed to be mainly controlled by the dissolution rate of the complex above a pK(a) of PAA (4.75) and by the diffusion rate below the pK(a). The prepared complex appears to be an adequate carrier for the mucoadhesive drug delivery system.

Acrylic Resins↗

Effects of polyether-modified poly(acrylic acid) microgels on doxorubicin transport in human intestinal epithelial Caco-2 cell layers.

Novel microgels composed of cross-linked copolymers of poly(acrylic acid) and Pluronics were evaluated as possible permeation enhancers for doxorubicin transport using Caco-2 cell monolayers as a gastrointestinal model. Pluronic, triblock copolymers of ethylene oxide (EO) and propylene oxide (PO), were chosen to represent the most hydrophobic (Pluronic L61 and L92 with average compositions of EO(3)PO(30)EO(3) and EO(8)PO(52)EO(8), respectively) and the relatively hydrophilic (Pluronic F127 with average formula EO(99)PO(67)EO(99)) extremes of this class of block copolymers. The weight ratio of Pluronic to poly(acrylic acid) in the microgels was set at 45:55. By inhibiting the P-glycoprotein (P-gp)-mediated doxorubicin efflux from the cells and enhancing the passive influx, the microgels were shown to enhance the overall cell absorption of doxorubicin. The enhancement effect was more pronounced than with a known penetration enhancer, Pluronic L61, and was comparable to that of Pluronic L92. Microgels exhibited synergism of the doxorubicin transport enhancement with Verapamil, a known inhibitor of the P-gp. The effects of the microgels were studied using the hydrophilic marker ([14C]mannitol) test and the MTT assay. Transepithelial electrical resistance (TEER) studies demonstrated that the microgels decreased TEER to about 80% of initial values, but these minor effects were fully reversible, indicating viability of the cells after incubation with microgels. No significant enhancement of [14C]mannitol transport by microgels was observed, relative to Carbopol 934NF (control polymer). Cytotoxicity studies confirmed that the transport-enhancing properties of the microgels were not due to damage of the Caco-2 cell monolayers.

ATP Binding Cassette Transporter, Subfamily B↗

Inhalation toxicity of acrylic acid.

Male and female Fischer 344 rats and B6C3F1 mice were exposed to 0, 5, 25 or 75 ppm acrylic acid vapors 6 hours per day, 5 days per week, for 13 weeks. These exposure levels were selected after conducting a 2-week probe study in which 225 ppm caused pronounced growth retardation and nasal lesions in both rats and mice. The 13-week exposures had no adverse effect on the growth of male and female rats and male mice. However, mean body weight gains of female mice in the 25 and 75 ppm exposure groups were statistically significantly lower than for controls after 12 weeks of exposure. There were no pronounced treatment related effects on organ weights, hematologic parameters, clinical chemistry parameters or urinary parameters. Histopathologic examinations revealed lesions of the nasal mucosa in rats in the 75 ppm exposure group, and in some or all mice at each treatment level. The nasal lesions were primarily localized to the olfactory epithelium; the respiratory epithelium was relatively unaffected. The histopathologic observations in both rats and mice included degeneration, and inflammatory cell infiltration in the olfactory mucosa. In mice there were also instances of hyperplasia of the submucosal glands and, replacement of olfactory epithelium by respiratory epithelium. These effects were attributed to the irritant properties of acrylic acid vapors.

Acrolein↗

Acrylic prosthesis of the fifth cervical vertebra in cervical chordoma. Case report and review of the literature.

Description of a two-stage surgical treatment of a case of chordoma of the fifth cervical vertebra mainly affecting the vertebral body. In the first stage the cervical column was immobilized employing a posterior approach and a small portion of the tumour in the right lamina was removed. In the second stage the whole of the body of C5 was removed by an anterior route and replaced with an acrylic prosthesis. The advantages of acrylic resin and the literature on vertebral prostheses are discussed.

Acrylic Resins↗

Comparison and evaluation of the synthetic biopolymer poly-L-aspartic acid and the synthetic "plastic" polymer poly-acrylic acid for use in metal ion-exchange systems.

Poly-L-aspartic acid (PLAsp), a biopolymer, and a similar synthetic polymer, poly-acrylic acid (PAA), each consisting of approximately 50 repeating Asp and acrylic acid monomers, respectively, were immobilized onto controlled pore glass (CPG) and evaluated for use as metal ion-exchange materials. Both polymers achieve metal complexation primarily through their repeating carboxylate side groups resulting in a similar binding trend for the metals tested (Ca(2+), Cd(2+), Co(2+), Cu(2+), Mg(2+), Mn(2+), Na(+), Ni(2+), Pb(2+)), with metal binding capacities ranging from <0.1 to 12 micromol metal/g column and <0.1 to 32 micromol metal/g column for PLAsp and PAA respectively. Cu(2+) and Pb(2+) exhibited strong binding to both materials, while the other metals demonstrated only weak or minimal binding. Both columns allowed for quantitative release of bound metals through acid stripping and experienced increased overall metal binding with increasing pH. Both systems also maintained similar structural and chemical stability when continuously exposed to neutral buffered, highly acidic, oxidizing, large molecule rich, and elevated temperature environments. The main differences between the two systems are the material cost and system biodegradability.

Acrylates↗

Quantitative determination of BMS-186716, a thiol compound, in rat plasma by high-performance liquid chromatography-positive ion electrospray mass spectrometry after hydrolysis of the methyl acrylate adduct by the native esterases.

During method development in support of non-clinical studies in animal models, BMS-186716 was found to be extremely unstable in blood and plasma. Stabilization of the compound was achieved by reacting the compound with methyl acrylate (MA) in blood, from which the plasma was then prepared. While the resulting BMS-186716-MA adduct was found to be stable in dog plasma, and hence it was used as the basis for the method developed for analysis of dog plasma samples, the BMS-186716-MA adduct was found to be unstable in rat plasma as it was readily hydrolyzed to BMS-186716-acrylic acid (AA) by native esterases found in rat plasma. Although the finding of the instability of BMS-186716-MA in rat plasma was not the result of prospective planning, we were able to successfully develop a quantitative bioanalytical method using BMS-186716-AA as the analyte instead of the originally planned BMS-186716-MA analyte. The standard and quality-control (QC) samples were prepared by spiking blank plasma with BMS-186716-MA, and then allowing them to stand at room temperature for 1 h to convert BMS-186716-MA to BMS-186716-AA. After adding the internal standard BMS-188035-AA, each sample was acidified with HCl and then extracted with methyl tert.-butyl ether. The reconstituted extract was injected into a HPLC-electrospray ionization mass spectrometric system for detection by positive ion electrospray ionization. A lower limit of quantitation (LLQ) of 5 ng/ml was achieved, using 0.1 ml plasma and a standard curve range of 5-5000 ng/ml.

Acrylates↗

An investigation of mucus/polymer rheological synergism using synthesised and characterised poly(acrylic acid)s.

A range of poly(acrylic acid)s with different average degrees of polymerisation and cross-linking densities were synthesised using a solution polymerisation process. The rheological characteristics of aqueous dispersions of these materials and those of mixtures with homogenised pigs gastric mucus were investigated using dynamic oscillatory rheology, and compared to the known mucoadhesive Carbopol 934P. From the storage moduli, the rheological synergy and relative rheological synergy were calculated, and the effects of concentration and pH on this considered. Generally, the larger the molecular weight (and degree of cross-linking), the greater the rheological synergy, with Carbopol 934P giving the most pronounced effect. Rheological synergy was seen to be concentration-dependent, and a maximum concentration to produce an optimum effect was evident. Acid pHs were seen to favour synergy, although in marked contrast to previous literature reports, the optimum mucus-polymer interaction was not observed at the half ionised value (pH = pKa) but at pH regimes that were unique to each polymer type. This could be influenced by the structural constrains imposed on potential hydrogen bonded interactions. It was concluded that synthesising poly(acrylic acid)s with better defined physicochemical properties than commercially available polymers will advance the study of the phenomenon of rheological synergy.

Acrylic Resins↗

An in vitro model for investigating the gastric mucosal retention of 14C-labelled poly(acrylic acid) dispersions.

Polymers that bind from solution onto gastric mucosae can be used as a means of facilitating localised drug delivery, or act as therapeutic agents in their own right (e.g. by forming a protective layer or by inhibiting enzymes). Previous workers have used semi-quantitative methods to identify the ability of commercially available poly(acrylic acid)s to bind to gastric mucosa. In this study, the binding and retention of labelled poly(acrylic acid)s to sections of gastric mucosa from the pyloric region of pigs stomach were evaluated using 'static' and 'dynamic flow' test systems. Dispersions (3%) of 'low', 'high' and 'ultra high' (cross-linked) polymers were seen to adhere to porcine pyloric mucosa after exposure and rinsing in the 'static' system. The high molecular weight polymer showed the greatest retention in the 'dynamic' test system when washing continuously with simulated gastric acid. Changing the pH of the dispersions from 4.3 to 6.2 had little effect on polymer retention. It was concluded that polymers that were sufficiently mobile in solution to spread on, and interact with, the mucosal surface, but had a sufficiently high molecular weight to form viscous solutions and/or bioadhere to the mucosa, may be retained on the mucosal surface for the longest periods.

Acrylic Resins↗

Poly(acrylic acid) microspheres containing beta-cyclodextrin: loading and in vitro release of two dyes.

Microspheres containing poly(acrylic acid) and beta-cyclodextrin or maltose were prepared by a w/o solvent evaporation technique. The dispersed aqueous phase contained poly(acrylic acid) (800 mg) and beta-cyclodextrin or maltose (0, 200 or 800 mg). Food-grade olive oil was the continuous phase. Microsphere particle size was consistently between 15 and 25 microm, and carbohydrate content was in good agreement with that added to the dispersed phase in all cases. Two dyes, phenolphthalein and rhodamine B, having different solubility characteristics and strengths of association with beta-cyclodextrin, were selected for loading and in vitro release studies. Microspheres were loaded by soaking in a saturated propan-2-ol solution of the appropriate dye (6 h). Microsphere dye content ranged between 2.8 and 4.8 mg/g microspheres for phenolphthalein and between 2.2 and 3.7 mg/g for rhodamine B. Release studies were performed in phosphate buffer (pH 7.4; 37 degrees C). No difference in the release profile of either dye was observed between microspheres. The failure of microspheres containing beta-cyclodextrin in particular, to alter the in vitro release kinetics of either dye may be due to a number of factors and include: (i) limited cross-linking giving rise to a the rapid hydration of the polymer matrix; (ii) perturbation of the dye-beta-cyclodextrin complex by oil and/or organic solvent residues; and (iii) conformational changes/steric hindrance of the beta-cyclodextrin cavity (due to its covalent binding with PAA) resulting in a reduction in its ability to form inclusion complexes.

Acrylic Resins↗

Effect of round-edged acrylic intraocular lenses on preventing posterior capsule opacification.

PURPOSE: To clarify the extent to which the adhesiveness of an acrylic material influences the formation of posterior capsule opacification (PCO). SETTING: Jinshikai Medical Foundation, Nishi Eye Hospital, Osaka, Japan. METHODS: Two types of AcrySof(R) intraocular lenses (IOLs) were prepared: round edged and tumbled. The AcrySof with round edges was implanted in 1 eye in a group of 4 rabbits and the tumbled IOL, in 1 eye in a group of 5 rabbits. In both groups, the contralateral eye received a conventional AcrySof with sharp optic edges. A histopathological examination was performed 3 weeks after surgery. RESULTS: With the round-edged AcrySof IOL, no capsular bend formed at the optic edge and abundant lens epithelial cells (LECs) migrated posteriorly. With the sharp-edged AcrySof lens, a sharp capsular bend formed and LEC migration was significantly inhibited. In eyes with a tumbled IOL, a capsular bend was created, but it was less marked than that created by the sharp-edged lens and there was slightly more LEC migration posteriorly. CONCLUSIONS: The AcrySof IOL lost its preventive effect on PCO when the optic was rounded. The effect of the AcrySof lens in preventing PCO is mainly a result of its rectangular, sharp-edged optic design. The acrylic material may play a complementary role by helping create a sharp capsular bend. Capsular bend formation is the key to the PCO preventive effect of an IOL.

Acrylic Resins↗