Biomedical subjects

J M Bezemer

Publications and source records attributed to J M Bezemer.

9 recordsLinked to original sources

PubMed2002

Control of vitamin B12 release from poly(ethylene glycol)/poly(butylene terephthalate) multiblock copolymers.

The release of vitamin B12 (1355 Da) from matrices based on multiblock copolymers was studied. The copolymers were composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Vitamin B12 loaded films were prepared by using a water-in-oil emulsion method. The copolymer properties, like permeability, could be varied by increasing the PEG-segment length from 300 up to 4,000 g/mol and by changing the wt% of PEGT. From permeation and release experiments. the diffusion coefficient of vitamin B12 through PEGT/PBT films of different compositions was determined. The diffusion coefficient of Vitamin B12 was strongly dependent on the composition of the copolymers. Although an increased wt% of PEGT (at a constant PEG-segment length) resulted in a higher diffusion coefficient, a major effect was observed at increasing PEG-segment length. By varying the copolymer composition, a complete release of vitamin B12 in 1 day up to a constant release for over 12 weeks was obtained. The release rate could be effectively tailored by blending copolymers with different PEG-segment lengths. The swelling and the crystallinity of the matrix could explain the effect of the matrix composition on the release behavior.

Biocompatible Materials↗

PubMed2002

Bone growth in biomimetic apatite coated porous Polyactive 1000PEGT70PBT30 implants.

We recently, developed a simple one-day one-step incubation method to obtain bone-like apatite coating on flexible and biodegradable Polyactive 1000PEGT70PBT30. The present study reports a preliminary biological evaluation on the coated polymer after implantation in rabbit femurs. The porous cylindrical implants were produced from a block fabricated by injection molding and salt leaching. This technique provided the block necessary mechanical integrity to make small cylinders (diameter 3.5 x 5 mm2) that were suitable for implantation in rabbits. The coating continuously covered the surface of the polymer, preserving the porous architecture of outer contour of the cylinders. Two defects with a diameter of 3.5 or 4 mm were drilled in the proximal and distal part of femur diaphysis. The implants were inserted as press-fit or undersized into the cortex as well as in the marrow cavity. The polymer swelled after implantation due to hydration, leading to a tight contact with the surrounding bone in both defects. The adherence of the coating on the polymer proved to be sufficient to endure a steam sterilization process as well as the 15% swelling of the polymer in vivo. The coated Polyactive 1000PEGT70PBT30 has a good osteoconductive property, as manifested by abundant bone growth into marrow cavity along the implant surface during 4-week implantation. A favorable bioactive effect of the coating with an intimate bone contact and extensive bone bonding with this polymer was qualitatively confirmed. Concerning the bone ingrowth into the porous implant in the defect of 4 mm diameter, only marginal bone formation was observed up to 8 weeks with a maximal penetration depth of about 1 mm. The pore interconnectivity is important not only for producing a coating inside the porous structure but also for bone ingrowth into this biodegradable material. This preliminary study provided promising evidence for a further study using a bigger animal model.

Animals↗

PubMed2000

Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 2. Modulation of release rate.

Amphiphilic multiblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were used as matrix material for protein-loaded microspheres. The efficiency of lysozyme entrapment by a double emulsion method was found to depend on the swelling behavior of the polymers in water and decreased from 100% for polymers with a degree of swelling of less than 1.8 to 11% for PEG-PBT copolymers with a degree of swelling of 3.6. The particle size could be controlled by varying the concentration of the polymer solution used in the microsphere preparation. An increase in the polymer concentration resulted in a proportional increase in the particle size. The in vitro release profiles of the encapsulated model protein lysozyme could be precisely tailored by variation of the copolymer composition and the size of the microspheres. Both a slow continuous release of lysozyme, and a fast release which was completed within a few days could be obtained. The release behavior, attributed to a combination of diffusion and polymer degradation, could be described by a previously developed model.

Algorithms↗

PubMed2000

Microspheres for protein delivery prepared from amphiphilic multiblock copolymers. 1. Influence of preparation techniques on particle characteristics and protein delivery.

The entrapment of lysozyme in amphiphilic multiblock copolymer microspheres by emulsification and subsequent solvent removal processes was studied. The copolymers are composed of hydrophilic poly(ethylene glycol) (PEG) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks. Direct solvent extraction from a water-in-oil (w/o) emulsion in ethanol or methanol did not result in the formation of microspheres, due to massive polymer precipitation caused by rapid solvent extraction in these non-solvents. In a second process, microspheres were first prepared by a water-in-oil-in-water (w/o/w) emulsion system with 4% poly(vinyl alcohol) (PVA) as stabilizer in the external phase, followed by extraction of the remaining solvent. As non-solvents ethanol, methanol and mixtures of methanol and water were employed. However, the use of alcohols in the extraction medium resulted in microspheres which gave an incomplete lysozyme release at a non-constant rate. Complete lysozyme release was obtained from microspheres prepared by an emulsification-solvent evaporation method in PBS containing poly(vinyl pyrrolidone) (PVP) or PVA as stabilizer. PVA was most effective in stabilizing the w/o/w emulsion. Perfectly spherical microspheres were produced, with high protein entrapment efficiencies. These microspheres released lysozyme at an almost constant rate for approximately 28 days. The reproducibility of the w/o/w emulsion process was demonstrated by comparing particle characteristics and release profiles of three batches, prepared under similar conditions.

Drug Compounding↗

PubMed2000

Control of protein delivery from amphiphilic poly(ether ester) multiblock copolymers by varying their water content using emulsification techniques.

Protein-containing films and microspheres, based on poly(ethylene glycol)-poly(butylene terephthalate) (PEG-PBT) multiblock copolymers, were prepared from water-in-oil (w/o) emulsions. The properties of the matrices could be controlled by the water-to-polymer ratio (w/p) in the w/o emulsion. A linear increase in water uptake of the matrices was observed with increasing emulsion w/p. This could be explained by an increase in the number of dispersed water-rich domains in the polymer matrix. At low volume fraction of the dispersed phase (epsilon), lysozyme release was mainly dependent on the permeability of the swollen polymer bulk. Above a critical volume fraction (the percolation threshold epsilon(c)), the dispersed water-rich phase formed an interconnected network, which largely enhanced the permeability of the matrix. Determination of the permeability of PEG-PBT matrices for vitamin B(12) as a function of epsilon confirmed the formation of such an interconnected network. This interconnected network could be used to achieve controlled release of a large protein (bovine serum albumin, BSA) from PEG-PBT films and microspheres. Due to its hydrodynamic diameter, BSA was screened by the polymer network when epsilon was low. However above epsilon(c), the fraction released BSA increased with increasing volume fraction of the dispersed phase. A very rapid BSA release could be obtained, with the majority of the incorporated BSA released within 1 day, as well as a slow and continuous release, lasting for over 150 days. When BSA-containing microspheres were prepared with a volume fraction just below the percolation threshold, a delayed release was observed. This was attributed to the effect of polymer degradation on matrix permeability.

Drug Delivery Systems↗

PubMed2000

Zero-order release of lysozyme from poly(ethylene glycol)/poly(butylene terephthalate) matrices.

Protein release from a series of biodegradable poly(ether ester) multiblock copolymers, based on poly(ethylene glycol) (PEG) and poly(butylene terephthalate) (PBT) was investigated. Lysozyme-containing PEG/PBT films and microspheres were prepared using an emulsion technique. Proteins were effectively encapsulated and dense polymer matrices were formed. The swelling in water of PEG/PBT films reached equilibrium within 3 days. The degree of swelling increased with increasing PEG content and with increasing molecular weight of the PEG segment. The release rate of lysozyme from PEG/PBT films could be tailored very precisely by controlling the copolymer composition. Release rates increased with increasing PEG/PBT weight ratio and increasing molecular weight of the PEG segment. For films prepared from block copolymers with PEG blocks of 4000 g/mol, first-order lysozyme release was observed. For matrices prepared from polymers with PEG segments of 1000 and 600 g/mol, the lysozyme release profile followed near zero-order kinetics. A mathematical description of the release mechanism was developed which takes into account the effect of polymer hydrolytic degradation on solute diffusion. The model was found to be consistent with the experimental observations. Finally, determination of the activity of released protein showed that lysozyme was not damaged during the formulation, storage and release periods.

Drug Stability↗

PubMed2000

Amphiphilic poly(ether ester amide) multiblock copolymers as biodegradable matrices for the controlled release of proteins.

Amphiphilic poly(ether ester amide) (PEEA) multiblock copolymers were synthesized by polycondensation in the melt from hydrophilic poly(ethylene glycol) (PEG), 1,4-dihydroxybutane and short bisester-bisamide blocks. These amide blocks were prepared by reaction of 1,4-diaminobutane with dimethyl adipate in the melt. A range of multiblock copolymers were prepared, with PEG contents varying from 23-66 wt %. The intrinsic viscosity of the PEEA polymers varied from 0.58-0.78. Differential scanning calorimetry showed melting transitions for the PEG blocks and for the amide-ester blocks, suggesting a phase separated structure. Both the melting temperature and the crystallinity of the hard amide-ester segments decreased with increasing PEG content of the polymers. The equilibrium swelling ratio in phosphate buffered saline (PBS) increased with increasing amount of PEG in the polymers and varied from 1.7 to 3.7, whereas the polymer that contained 66 wt % PEG was soluble in PBS. During incubation of PEEA films in PBS, weight loss and a continuous decrease in the resulting inherent polymer viscosity was observed. The rate of degradation increased with increasing PEG content. The composition of the remaining matrices did not change during degradation. A preliminary investigation of the protein release characteristics of these PEEA copolymers showed that release of the model protein lysozyme was proportional to the square root of time. The release rate was found to increase with increasing degree of swelling of the polymers.

Biocompatible Materials↗

PubMed1999

A controlled release system for proteins based on poly(ether ester) block-copolymers: polymer network characterization.

The properties of a series of multiblock copolymers, based on hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(butylene terephthalate) (PBT) blocks were investigated with respect to their application as a matrix for controlled release of proteins. The degree of swelling, Q, of the copolymers increased with increasing PEG content and with increasing molecular weight of the PEG segment. Within the composition range tested, Q varied from 1.26 for polymers with PEG segments of 600 g/mol and a PBT content of 60 weight.% up to 3.64 for polymers with PEG segments of 4000 g/mol and a PEG/PBT weight ratio of 80:20. Equilibrium stress (compression)-strain measurements were performed in order to estimate mesh sizes. The mesh size of the copolymers ranged from 38 to 93 A, which was experimentally confirmed by diffusion of vitamin B(12) (hydrodynamic diameter d(h)=16.6 A), lysozyme (d(h)=41 A) and bovine serum albumin (d(h)=72 A). The in vitro degradation of PEG/PBT copolymers with a PEG block length of 1000 g/mol and PEG/PBT weight ratios of 70:30, 60:40 and 40:60 was studied. Matrices with increasing PEG contents exhibited a faster weight loss in phosphate-buffered saline (pH 7.4) at 37 degrees C. Over a degradation period of 54 days, M(n) decreased by about 35-45%, while the composition of the matrices, determined by NMR, remained almost constant.

Animals↗

PubMed1996

Poly(ethylene oxide)-modified carboxylated polystyrene latices--immobilization chemistry and protein adsorption.

alpha,omega-Diamino poly(ethylene oxides) (PEOs) with different molecular weights (148, 1000, and 3400) were covalently immobilized onto carboxylated polystyrene latices. The immobilization of PEO was carried out with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS) in aqueous media. The reaction conditions were optimized to obtain a maximal coupling of PEO. The degree of coupling was determined by the surface concentration of amino groups. The maximal surface concentrations of amino groups were close to what is expected for a complete coverage of the surface with PEO. Adsorption of albumin from a buffer solution onto PEO-containing surfaces was about 85% less than the albumin uptake by unmodified polystyrene latices. Protein adsorption from plasma dilutions was lower on surfaces containing PEO molecules with a higher molecular weight. The reduction of the protein uptake from plasma by surfaces containing PEO-3400 molecules was only 40% compared to the adsorption to unmodified surfaces. These results indicate that plasma proteins have a low affinity for surfaces modified with PEO. However the PEO modified surfaces are by no means 'protein resistant' when exposed to plasma.

Adsorption↗