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PubMed1998

Effect of interparticulate interaction on release kinetics of microsphere ensembles.

The release kinetics of microsphere ensembles is complicated by the mutual influence of the microspheres which are entrapped in small compartments such as body cavities. This work focused on the effect of interparticulate interaction on the release kinetics of microsphere ensembles with limited spreading. Experiments and finite element modeling were conducted to investigate diffusional drug release from a single sphere, a monolayer, and multiple layers of microspheres. Poly(methyl methacrylate-co-methacrylic acid) (P(MMA/MAA)) microspheres and azidothymidine (AZT) were used in the experiments. The order of the release rate of AZT from various microsphere populations was observed to be single sphere > monolayer > multiple layers. This evidenced the importance of interparticulate interaction. The finite element simulations elucidated the influence of various factors on the release kinetics of microsphere ensembles including the separation distance, location of the spheres, and the drug accumulation in the medium. Calibration of overall release kinetics for the neighboring effect was proposed on the basis of the spreading factor. Overall release profiles of microsphere ensembles were predicted using the release profiles of individual microspheres at various locations.

Diffusion↗
PubMed1982

The influence of gel formulation on the diffusion of salicylic acid in polyHEMA hydrogels.

The influence of solute concentration, gel hydration, and crosslinking density on diffusion rates in polyHEMA hydrogels has been investigated using a radio-tracer technique. At hydrations above 31% water, diffusion is by pore flow, and increases in the crosslinking density of gels bring about a decrease in the diffusion coefficient, D. Below 31% hydration, diffusion is predominantly by solution diffusion and changes in crosslinking density have little effect on the diffusion coefficient. The diffusion coefficient is invariant with solute concentration within the range reported, although a very high solute concentration, for the gels of lower hydration, the diffusion coefficient is higher than expected. A high value for D may be due to saturation of the binding sites of the diffusant on the polymer chains, leaving a greater proportion of diffusant available for transport.

Diffusion↗
PubMed2004

Preparation of fluorescent particles with long excitation and emission wavelengths dispersible in organic solvents.

We introduce a fast and simple one-step method, a variation of the methods of Barrett and Campbell and Bartlett, to synthesize monodisperse fluorescent particles that can be dispersed in organic solvents and have long excitation (649 nm) and emission wavelengths (679 nm). A lipophilic fluorescent dye, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate, is directly incorporated into PMMA particles through dispersion polymerization. A poly(hydroxystearic acid) graft (poly) methyl methacrylate (MM) and methacrylic acid (MA) copolymer is used as a stabilizer to prevent the particles from aggregating and flocculating in the nonaqueous solvents. The fluorescent PMMA particles are very uniform in size, bleach at very low rate, and behave like hard spheres in their ordering on substrates. One important achievement in our synthesis protocol is that we are able to produce particles of a desired size by choosing the composition of the reactants according to a predetermined relationship between particle size and composition of reactants. In addition, the effects of fluorescent dye and polar solvent (ethanol) on the formation and size of particles are discussed.

Biocompatible Materials↗
PubMed1995

Prolonged blood circulation in rats of nanospheres surface-modified with semitelechelic poly[N-(2-hydroxypropyl)methacrylamide].

Semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]s (ST-PHPMA) containing one amino end-group and differing in molecular weight were synthesized by radical polymerization in the presence of 2-aminoethanethiol (AET) as chain transfer agent. These polymers were covalently attached via amide bonds to the surface of nanospheres based on a copolymer of methyl methacrylate, maleic anhydride, and methacrylic acid. When compared to unmodified nanospheres, those with the surface modified with ST-PHPMA possessed a decreased protein (albumin, IgG, fibrinogen) adsorption in vitro, an increased intravascular half-life as well as a decreased accumulation in the liver after intravenous administration into rats. The higher the molecular weight of the ST-PHPMA, the more pronounced the changes in these properties. The results obtained have clearly demonstrated that covalently attached ST-PHPMA chains are efficient in decreasing the biorecognition of negatively charged (hydrophilic) polymer surfaces.

Acrylic Resins↗
PubMed2002

Morphology of poly(methacrylic acid)/poly(N-isopropyl acrylamide) interpenetrating polymeric networks.

The morphology of interpenetrating polymeric networks (IPNs) composed of the temperature-sensitive poly(N-isopropyl acrylamide) (PNIPAAm) and the pH-sensitive poly(methacrylic acid) (PMAA) were investigated by scanning electron microscopy (SEM). The IPN hydrogels were prepared by a sequential UV polymerization method. SEM studies were conducted on IPN hydrogel samples dried by different methods, and the influence on the IPN structure was discussed. The environmental conditions induced morphological changes for these dual sensitive IPN hydrogels which were studied by cryogenic SEM, when the gels were analyzed in their wet state. The results showed that the porous size in the IPN was strongly influenced by the environmental pH and temperature. Decrease in pH and increase in temperature resulted in significant pore size decrease for the swollen IPNs hydrogels.

Acrylic Resins↗
PubMedDate not supplied

Microencapsulated Eudragit RS30D-coated controlled-release pellets: the influence of dissolution variables and topographical evaluation.

The air suspension technique was employed to prepare Eudragit RS30D-coated controlled-release pellets of salbutamol. Drug release in dissolution studies can be dependent on the dissolution method and medium used. Thus, the aim of this study was to investigate the influence of various dissolution methods and dissolution medium pH values on drug release from a batch of pellets which displayed controlled drug-release characteristics over an 8-h period in deionized water using the rotating basket method. In vitro testing using the official USP XXII (rotating basket and rotating paddle) and non-official (rotating bottle) methods showed drug release to be independent of the method used. The prepared pellets displayed pH-dependent drug-release characteristics when tested in hydrochloric acid (pH 1.5), phosphate buffer (pH 6.8) and deionized water (pH 7.2). Also, in vitro testing, which exposed the pellets to a changing pH gradient that simulated the gastrointestinal pH conditions following oral administration, was used to confirm the drug-release characteristics. The results showed controlled-release characteristics to be maintained, with the drug being released over an 8-h period. Scanning electron microscopic evaluation proved useful in the elucidation of the physical characteristics of the controlled-release pellets as well as in the identification of a possible mode of drug transfer into the dissolution medium.

Acrylic Resins↗
PubMed1989

[Preliminary study of mechanism of HFMC inhibiting sperm functions].

In this study, the mechanism of HFMC (copolymer of hydroxyethyl methacrylate-methacrylic acid-ethyl methacrylate) inhibiting sperm functions was investigated in vitro. We found that HFMC could decrease the pH value of sperm suspension with an increase in HFMC concentration to a certain extent but the maximum decrease is no more than a value of 2.5. The inhibitory effects of HFMC on the sperm functions could be partly inverted after the pH values of sperm suspension had been shifted to its original level of pH 7.4 by the addition of proper amounts of basic solution. It is suggested that the descent of pH value may be one of the causes of HFMC inhibiting sperm functions.

Acrylates↗
PubMed1977

Mathematical model for enteric film coating of tablets.

The enteric film coating of placebo tablets, using a methacrylic acid-methyl methacrylate copolymer as the film former in the coating solution, was studied by statistical techniques. The effects of four independent formulation and process variables on the disintegration time of the coated film in simulated intestinal fluid and on the resistance to disintegration of the coated film in simulated gastric fluid were studied. The results of a statistically designed set of experiments were used as the input data. Regression analysis of these data resulted in two first-order polynomial equations. The linear model obtained for the disintegration time of the coating in the simulated intestinal fluid was analyzed by the steepest descent method to determine the most suitable combination of the independent variables.

Chemistry, Pharmaceutical↗
PubMed2003

A physico-chemical approach of polyanion-polycation interactions aimed at better understanding the in vivo behaviour of polyelectrolyte-based drug delivery and gene transfection.

Polyanions and polycations are known to interact electrostatically and form soluble or insoluble polyelectrolyte complexes. Body fluids, blood and cells are composed of many polyelectrolytic systems such as proteins, glycoproteins, poly(glycosamino glycane)s, polynucleotides, etc. under physiological conditions. Nowadays synthetic polyelectrolytes are proposed as carriers of bioactive compounds, such as drugs and genes, and are thus to be injected into body fluids. For the sake of better understanding the complex behaviour of such artificial polyelectrolytic systems in the pool of natural polyelectrolytes forming living systems, interactions of bi- and multi-components mixtures of synthetic polyanions with the same synthetic polycation, namely poly[(dimethylaminoethyl) methacrylate], HCl, were investigated under the conditions imposed by physiological media, namely pH = 7.4, ionic strength mu = 0.15 and T = 37 degrees C. The selected artificial polyanions were the sodium salts of poly(acrylic acid), poly(methacrylic acid), poly(L-lysine citramide) and poly(styrene sulfonic acid) which have different acid strength, charge density and ionogenic group. The influence of ionic strength and pH on complex formation and stability was investigated by turbidimetry at lambda = 520 nm. Phase separation occurred regardless of ionic strength in the case of sodium polystyrene sulfonate. For the other polyanions, redissolution was observed at critical NaCl concentrations much higher than the physiological ionic strength. In the case of mixtures of two or three polyanions with the polycation, the complex formation appeared polyanion-selective at physiological ionic strength. Data are discussed with regard to phenomena that can occur in vivo.

Acrylic Resins↗
PubMed1995

Silicone rubber-hydrogel composites as polymeric biomaterials. VI. Transport properties in the water-swollen state.

Permeation of inorganic salts in water-swollen silicone rubber-hydrogel composites consisting of a silicone rubber matrix and lightly cross-linked particles of poly(2-hydroxyethyl methacrylate), poly(2-hydroxyethyl methacrylate-co-methacrylic acid), poly(methacrylic acid), polyacrylamide or poly(acrylamide-co-methacrylic acid) hydrogels was investigated. The results, together with earlier data on permeation of non-ionic low-molecular-weight substances through the composite materials, were evaluated in terms of the free-volume diffusion theory. It was found that the materials with water content exceeding a certain limit are highly permeable to the salts, and that, as regards permeation properties, they behave as homogeneous water-swollen hydrogels. The dependence of electrical conductivity of the water-swollen composites on the hydrogel phase content was measured, and the results are discussed in relation to other transport properties and to the structure of the materials.

Acrylic Resins↗
PubMed1999

Functionalized nanoparticles for endotoxin binding in aqueous solutions.

Nanoparticles consisting of a polystyrene core and a polyglycidyl methacrylate shell were prepared by a two-step emulsion polymerization. The size and surface properties of the particles were characterized by scanning electron microscopy, dynamic light scattering and polyelectrolyte titration techniques. Particles were found to be monodisperse with a mean diameter of about 85 nm. Parent particles were modified with a number of different ligands including diamines of increasing chain length, amino acids and corresponding amines and higher molecular weight ligands like polymyxin B. The modified particles were tested for their endotoxin (ET) binding capacity in water and physiological sodium chloride solution with the Limulus amebocyte lysate (LAL) assay. It was found that the ET binding properties of the different ligands depend both on the ability of the ligand to form Coulomb- and van der Waals-interactions with the ET molecule influenced by the nature of the suspension medium. Therefore, the choice of ligands for particle modification has to consider minutely the conditions under which ET has to be removed, e.g. removal from pure water, dialysis fluids, plasma or blood.

Biocompatible Materials↗
PubMed2004

Physicochemical characterization of degradable thermosensitive polymeric micelles.

Amphiphilic AB block copolymers consisting of thermosensitive poly(N-(2-hydroxypropyl) methacrylamide lactate) and poly(ethylene glycol), pHPMAmDL-b-PEG, were synthesized via a macroinitiator route. Dynamic light scattering measurements showed that these block copolymers form polymeric micelles in water with a size of around 50 nm by heating of an aqueous polymer solution from below to above the critical micelle temperature (cmt). The critical micelle concentration as well as the cmt decreased with increasing pHPMAmDL block lengths, which can be attributed to the greater hydrophobicity of the thermosensitive block with increasing molecular weight. Cryogenic transmission electron microscopy analysis revealed that the micelles have a spherical shape with a narrow size distribution. 1H NMR measurements in D2O showed that the intensity of the peaks of the protons from the pHPMAmDL block significantly decreased above the cmt, indicating that the thermosensitive blocks indeed form the solidlike core of the micelles. Static light scattering measurements demonstrated that pHPMAmDL-b-PEG micelles with relatively large pHPMAmDL blocks possess a highly packed core that is stabilized by a dense layer of swollen PEG chains. FT-IR analysis indicated that dehydration of amide bonds in the pHPMAmDL block occurs when the polymer dissolved in water is heated from below to above its cmt. The micelles were stable when an aqueous solution of micelles was incubated at 37 degrees C and at pH 5.0, where the hydrolysis rate of lactate side groups is minimized. On the other hand, at pH 9.0, where hydrolysis of the lactic acid side groups occurs, the micelles started to swell after 1.5 h of incubation and complete dissolution of micelles was observed after 4 h as a result of hydrophilization of the thermosensitive block. Fluorescence spectroscopy measurements with pyrene loaded in the hydrophobic core of the micelles showed that when these micelles were incubated at pH 8.6 and at 37 degrees C the microenvironment of pyrene became increasingly hydrated in time during this swelling phase. The results demonstrate the potential applicability of pHPMAmDL-b-PEG block copolymer micelles for the controlled delivery of hydrophobic drugs.

Acrylamides↗
PubMed1996

3-year clinical evaluation of modified Gluma adhesive systems in cervical abrasion/erosion lesions.

PURPOSE: To study the clinical performance of two candidates for improvement of the original Gluma bonding system. MATERIALS AND METHODS: Eight teeth with cervical buccal abrasion/erosion lesions were identified in 40 patients. The lesions were conditioned with an oxalic acid solution followed by either a HEMA-glutaraldehyde bonding agent or a formamide-containing bonding agent. The lesions were restored with a hybrid composite. Each patient received the same number of restorations with the two different bonding formulations. All restorations were made by the same operator (JK). Evaluations were based on the USPHS system. RESULTS: No difference between the two groups as to retention, marginal adaptation and discoloration was observed after 3 years. Eight restorations were lost and a slight increase in marginal discoloration was seen during the observation period.

Adult↗
PubMed1990

Hemolysis mechanism of dental adhesive monomer (methacryloyloxydecyl dihydrogen phosphate) using a phosphatidylcholine liposome system as a model for biomembranes.

To clarify the mechanism of interaction of dental adhesive monomers with biological membranes at the molecular level, we studied the interaction of methacryloyloxydecyl dihydrogen phosphate (MDP) and methacrylic acid (MAA) with the dipalmitoylphosphatidylcholine (DPPC) liposome system using NMR and DSC. MDP-DPPC interaction became apparent through broadening of the DPPC phase transition as pH decreased, finally the enthalpy of MDP-DPPC (1:1 mol ratio) reduced to zero at pH 2.5. Proton chemical shifts of MDP enhanced shielding and proton signals due to the phosphatidylcholine polar group (O-CH2-CH2-N bond) of DPPC were observed. MAA-DPPC interaction was smaller than that of MDP-DPPC, even at low pH. It was concluded that the strong hemolytic activity of MDP may be due to its interaction with the phospholipid bilayers of erythrocyte membranes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2002

Heparin release from slippery-when-wet guide wires for intravascular use.

Thin metallic wires with an adherent hydrophilic/ lubricious polymeric coating were manufactured in a new extrusion-like procedure. This procedure is part of a novel and efficient way of assembling lubricious guide wires for intravascular interventions, such as percutaneous transluminal angioplasty. It is reported that heparin can readily be incorporated in the hydrophilic coating. A set of heparin-containing guidewire models was made and studied in detail. This showed that (i). immersion of the guide-wire models in an aqueous environment leads to release of heparin from their surface; (ii). the presence of heparin in the coating does not impede the lubricity of the coils; (iii). addition of stearic acid in the coating, next to heparin, does not influence the lubricity of the guide-wire models. Two different charges of heparin (designated heparin-low and heparin-high) were incorporated in the coating. It is discussed that release of heparin from the surface of medical devices (e.g. guide wires and catheters) is much more effective than systemic heparinization, basically because dissolved heparin molecules have a much larger probability of simply passing a medical device's surface (axial convection) rather than contacting it (radial diffusion).

Angioplasty, Balloon↗
PubMed2006

Development of PEGDMA: MAA based hydrogel microparticles for oral insulin delivery.

An oral insulin delivery system based on copolymers of poly(ethylene glycol) dimethacrylate and methacrylic acid was developed and its functional activity was tested in non-obese diabetic rats. Poly(ethylene glycol) dimethacrylates (PEGDMA) were synthesized by esterification reaction of different molecular weight poly(ethylene glycol) with methacrylic acid (MAA) in presence of acid catalyst. PEG dimethacrylates of molecular weight ranging from 400 to 4000 and methacrylic acid were further copolymerized by suspension polymerization to obtain pH sensitive hydrogel microparticles. The diameter of poly(PEGDMA:MAA) microparticles increased with increasing the molecular weight of the poly(ethylene glycol) dimethacrylate used for respective microparticle synthesis. Insulin was loaded into the hydrogel microparticles by partitioning from concentrated insulin solution. In vitro release studies of insulin loaded microparticles were performed by simulating the condition of gastrointestinal tract, which showed the minimal insulin leakage (18-25%) at acidic pH (2.5) and significantly higher release at basic pH (7.4). Animal studies were carried out to investigate the abilities of the insulin loaded hydrogel microparticles to influence the blood glucose levels of the diabetic rats. In studies with diabetic rats, the blood glucose level reduced for animals that received the insulin loaded hydrogel microparticles and the effect lasted for 8-10h. It was also observed, two capsules per day of poly(PEGDMA4000:MAA) hydrogel microparticles containing 80 I.U./kg of insulin dose were sufficient to control the blood glucose level of fed diabetic rats between 100 and 300 mg/dl.

Acrylates↗
PubMed2004

In-tube solid-phase microextraction with poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary for direct high-performance liquid chromatographic determination of ketamine in urine samples.

Ketamine was used for anaesthesia originally but has emerged as an abused drug in recent years. The prevalence of ketamine abuse demands a direct and rapid determination method. It is known that in-tube solid phase microextraction (in-tube SPME) can perform extraction with a capillary linked directly to a HPLC system, providing an automated and accurate extraction procedure. In this paper, an in-tube SPME coupled to HPLC method was developed for the determination of ketamine in urine samples with a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column as the extraction phase, which is expected to provide higher extraction efficiency than open tubular capillaries. After optimizing the extraction conditions, ketamine was extracted directly from urine samples in a wide dynamic linear range of 50-10,000 ng mL(-1), with the detection limit obtained as 6.4 ng mL(-1). The intra-day and inter-day precision for the method was 1.6% and 1.7%, respectively. The urine samples from suspect addicts have been successfully analyzed within 20 min. The re-usability of the monolithic column was also confirmed as no decrease of the extraction efficiency was shown after urine extraction.

Chromatography, High Pressure Liquid↗
PubMed1997

The influence of Eudragit type on the dissolution rate of acetylsalicylic acid from matrix tablets.

The effect of four Eudragits used as matrix substances on the physical characteristics of tablets and on the dissolution rate of acetylsalicylic acid has been investigated. The concentration of matrix substance necessary for achieving the appropriate effect of sustained release of acetylsalicylic acid (ASA) depends on the type of Eudragit used. For tablets prepared using Eudragit RS-100, Eudragit L-100-55 and Eudragit S-100, the acceptable dissolution rate of ASA was obtained with only 3% of polymer. In the case of Eudragit RL-100, to obtain the same effect, 10% of polymer was required. The dissolution data were evaluated on the basis of theoretical dissolution equations and by linear transformation of dissolution curves. The following mathematical models were employed: zero order equation, first order kinetics, Hixon-Crowell's cube root kinetics and diffusion model. The results indicated that the fitness of the kinetic model was dependent on the type of Eudragit used.

Acrylic Resins↗