Biomedical subjects

M Malmsten

Publications and source records attributed to M Malmsten.

At least 19 recordsLinked to original sources

PubMed2004

The effect of garlic on arteriosclerotic nanoplaque formation and size.

OBJECTIVE: In an in vitro biosensor model (PCT/EP 97/05212), the interplay between different lipoproteins in arteriosclerotic nanoplaque formation, as well as aqueous garlic extract (0.2-5.0 g/l from LI 111 powder) as a possible candidate drug against arterio/atherosclerosis were tested within the frame of a high throughput screening. METHODS: The processes described below were studied by ellipsometric techniques quantifying the adsorbed amount (nanoplaque formation) and layer thickness (nanoplaque size). A thorough description of the experimental setup has been given previously. RESULTS: Proteoheparan sulfate (HS-PG) adsorption to hydrophobic silica was monoexponential and after approximately 30 min constant. The addition of 2.52 mmol/l Ca2+ led to a further increase in HS-PG adsorption because Ca2+ was bound to the polyanionic glycosaminoglycan (GAG) chains thus screening their negative fixed charges and turning the whole molecule more hydrophobic. Incubation with 0.2 g/l aqueous garlic extract (GE) for 30 min did not change the adsorption of HS-PG. However, the following addition of Ca2+ ions reduced the increase in adsorption by 50.8% within 40 min. The adsorption of a second Ca2+ step to 10.08 mmol/l was reduced by even 82.1% within the next 40 min. Having detected this inhibition of receptor calcification, it could be expected that the build-up of the ternary nanoplaque complex is also affected by garlic. The LDL plasma fraction (100 mg/dl) from a healthy probationer showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca2+ concentration, with a strong increase at higher Ca2+ concentrations. GE, preferably in a concentration of 1 g/l, applied acutely in the experiment, markedly slowed down this process of ternary aggregational nanoplaque complexation at all Ca2+ concentrations used. In a normal blood Ca2+ concentration of 2.52 mmol/l, the garlic induced reduction of nanoplaque formation and molecular size amounted to 14.8% and 3.9%, respectively, as compared to the controls. Furthermore, after ternary complex build-up, GE similar to HDL, was able to reduce nanoplaque formation and size. The incubation time for HDL and garlic was only 30 min each in these experiments. Nevertheless, after this short time the deposition of the ternary complex decreased by 6.2% resp. 16.5%, i.e. the complex aggregates were basically resolvable. CONCLUSIONS: These experiments clearly proved that garlic extract strongly inhibits Ca2+ binding to HS-PG. In consequence, the formation of the ternary HS-PG/LDL/Ca2+ complex, initially responsible for the 'nanoplaque' composition and ultimately for the arteriosclerotic plaque generation, is decisively blunted.

Arteriosclerosis↗

PubMed2003

Reduction of arteriosclerotic nanoplaque formation and size by fluvastatin in a receptor-based biosensor model.

Proteoheparan sulfate can be adsorbed onto a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques suggesting that HDL has a high binding affinity and a protective effect on interfacial heparan sulfate proteoglycan layers with respect to LDL and Ca(2+) complexation. LDL was found to be deposited strongly at the proteoheparan sulfate-coated surface, particularly in the presence of Ca(2+), apparently through complex formation 'proteoglycan-low density lipoprotein-calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. In a receptor-based biosensor application, this system was tested on its reliability to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The VLDL/IDL/LDL and VLDL/IDL/LDL/HDL plasma fractions from a high risk patient with dyslipoproteinaemia and type 2 diabetes mellitus showed the start of arteriosclerotic nanoplaque formation at a normal blood Ca(2+) concentration, with a strong increase at higher Ca(2+) concentrations. Nanoplaque formation and size of the HDL-containing lipid fraction remained well below that of the LDL-containing lipid fraction. Fluvastatin, whether applied acutely to the patient (one single 80 mg slow release matrix tablet) or in a 2-month medication regimen, markedly slowed down this process of ternary aggregational nanoplaque build-up and substantially inhibited nanoplaque size development at all Ca(2+) concentrations used. The acute action gave no significant change in lipid concentrations of the patient. Furthermore, after nanoplaque generation, fluvastatin, similar to HDL, was able to reduce nanoplaque formation and size. These immediate effects of fluvastatin have to be taken into consideration when interpreting the clinical outcome of long-term studies.

Adsorption↗

PubMed2003

The effect of an HMG-CoA reductase inhibitor on arteriosclerotic nanoplaque formation and size in a biosensor model.

Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques. Low-density lipoprotein (LDL) was found to deposit strongly at the proteoheparan sulfate-coated surface, particularly in the presence of Ca(2+), apparently through complex formation 'proteoglycan-LDL-calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. HDL bound to heparan sulfate proteoglycan protected against LDL deposition and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL was able to decelerate the ternary complex deposition and to disrupt newly formed nanoplaques. Therefore, HDL attached to its proteoglycan receptor sites is thought to raise a multidomain barrier, selection and control motif for transmembrane and paracellular lipoprotein uptake into the arterial wall. The molecular arteriosclerosis model was tested on its reliability in a biosensor application in order to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)/LDL and VLDL/IDL/LDL/HDL plasma fractions from a high-risk patient with dyslipoproteinemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca(2+) concentration, with a strong increase at higher Ca(2+) concentrations. Nanoplaque formation and size of the HDL-containing lipid fraction remained well below that of the LDL-containing lipid fraction. Fluvastatin, whether applied acutely to the patient (one single 80 mg slow release matrix tablet) or in a 2-months medication regimen, markedly slowed down this process of ternary aggregational nanoplaque build-up and substantially inhibited nanoplaque size development at all Ca(2+) concentrations used. The acute action resulted without any significant change in lipid concentrations of the patient. Furthermore, after nanoplaque generation, fluvastatin, similar to HDL, was able to reduce nanoplaque formation and size. These immediate effects of fluvastatin have to be taken into consideration while interpreting the clinical outcome of long-term studies.

Adsorption↗

PubMed2002

Biosensing of arteriosclerotic nanoplaque formation and interaction with an HMG-CoA reductase inhibitor.

Proteoheparan sulphate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. As a result of electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing one receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques suggesting that high-density lipoprotein (HDL) has a high binding affinity and a protective effect on interfacial heparan sulphate proteoglycan layers with respect to low-density lipoprotein (LDL) and Ca2+ complexation. Low-density lipoprotein was found to deposit strongly at the proteoheparan sulphate-coated surface, particularly in the presence of Ca2+, apparently through complex formation 'proteoglycan-LDL-calcium'. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulphate proteoglycan protected against LDL deposition and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL was able to decelerate the ternary complex deposition. Therefore, HDL attached to its proteoglycan receptor sites is thought to raise a multidomain barrier, selection and control motif for transmembrane and paracellular lipoprotein uptake into the arterial wall. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a 'nanoscopic' level under close to physiological conditions. In particular, Ca2+-promoted LDL deposition and the protective effect of HDL even at high Ca2+ and LDL concentrations agree well with previous clinical observations regarding risk and beneficial factors for early stages of atherosclerosis. Considering this, the system was tested on its reliability in a biosensor application in order to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)/LDL plasma fraction from a high risk patient with dyslipoproteinaemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca2+ concentration, with a strong increase at higher Ca2+ concentrations. Fluvastatin, whether applied to the patient (one single 80 mg slow release matrix tablet) or acutely in the experiment (2.2 micromol L-1), markedly slowed down this process of ternary aggregational nanoplaque complexation at all Ca2+ concentrations used. This action resulted without any significant change in lipid concentrations of the patient. Furthermore, after ternary complex build-up, fluvastatin, similar to HDL, was able to reduce nanoplaque adsorption and size. These immediate effects of fluvastatin have to be taken into consideration while interpreting the clinical outcome of long-term studies.

Adsorption↗

PubMed2001

Interactions between Local Anaesthetic Agents and Poly(N-isopropyl acrylamide) through Phase Behavior, Surface Tension, and Adsorption Measurement.

The interaction between the local anaesthetic agents prilocaine and lidocaine, on one hand, and poly(N-isopropyl acrylamide) (pNIPAM), on the other, is investigated through studies of the polymer phase behavior and through surface tension and adsorption measurements. In particular, the cloud points (CP) for pNIPAM in the presence of lidocaine and prilocaine under different conditions were compared to the effects of electrolytes and alcohols. It was found that the electrolytes affect the CP of pNIPAM in a lyotropic manner, whereas alcohols depress the CP of pNIPAM in an alkyl chain length dependent way; i.e., the longer the chain, the larger the decrease in CP. Lidocaine and prilocaine affect the CP of pNIPAM in a pH-dependent manner. Below the pK(a) of lidocaine and prilocaine, these cosolutes do not substantially affect the CP in the concentration range investigated, but rather behave analogous to simpler electrolytes. Above the pK(a), on the other hand, they strongly depress the CP already at low concentrations. In parallel, at low pH, the surface tension reduction due to lidocaine or prilocaine is marginal, whereas at high pH the surface tension is reduced considerably. Thus, the poor solubility of prilocaine and lidocaine at high pH causes these to become more surface active and simultaneously interact in a more pronounced way with pNIPAM. Furthermore, it was found from ellipsometry that an adsorbed pNIPAM layer contracts when lidocaine is added, presumably due to a lidocaine-pNIPAM interaction similar to that causing pNIPAM to phase separate. Analogous to this, it was demonstrated that an adsorbed pNIPAM layer shrinks and swells reversibly when the temperature is cycled above and beneath the CP. Copyright 2001 Academic Press.

Journal Article↗

PubMed2001

Physicochemical characterisation of a drug-containing phospholipid-stabilised o/w emulsion for intravenous administration.

Clomethiazole (CMZ) was used as a model drug to be incorporated into an emulsion vehicle. The effects of drug concentration and number of homogenisation steps were evaluated using multiple linear regression. The droplet size, measured as a z-average diameter by photon correlation spectroscopy (PCS), was found to be between 60 and 260 nm in the investigated range of CMZ concentrations, highly dependent on the concentration, but more weakly so on the number of homogenisation steps. Slow-scanning high-sensitivity differential scanning calorimetry (DSC) measurements showed that CMZ depresses the phospholipid chain melting temperature in the emulsion system, whereas (13)C nuclear magnetic resonance (NMR) experiments suggested that the CMZ molecules are to a large extent located in the surface region of the emulsion droplets. This interpretation is compatible with results from NMR self-diffusion measurements, which showed that most of the CMZ molecules are rapidly exchanged between emulsion droplets and the aqueous surrounding. It can be concluded that the surface-active drug CMZ has a significant influence on the characteristics of phospholipid-stabilised emulsions through its ability to interact with the phospholipid interface. Thus, the results underline the importance of characterising drug-lipid interactions for the development of lipid-based formulations.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2001

Local anaesthetic block copolymer system undergoing phase transition on dilution with water.

The possibility of formulating a local anaesthetic system displaying in situ gelation on dilution with water, as well as its dependence on concentration of active ingredients and pH was investigated. For this purpose Lutrol F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM were mixed in different ratios and investigated using crossed polarisers, small-angle X-ray diffraction, rheology, conductivity and NMR self-diffusion measurements. In particular, an isotropic phase of low viscosity turning into a high viscous hexagonal phase upon dilution with water was found. The increase in viscosity is only weakly dependent on temperature in the temperature range of 20-37 degrees C. The rheology and in vitro drug release of these systems were studied and the elastic modulus was found to be fairly independent of concentration of active ingredients and pH in the investigated region. The in vitro release of lidocaine and prilocaine was found to increase with increasing concentration of the active ingredients and with decreasing pH, the latter as a consequence of the pH-dependent ionisation of these substances. The behaviour of the system is promising from a pharmaceutical point of view, since the isotropic low-viscous phase can be injected into, e.g. a periodontal pocket where the presence of saliva will cause a temporal transition into a rigid hexagonal phase thus making the formulation stay at the application site. At even higher water content, either as a result of longer application time or rinsing with water, the hexagonal phase is effectively dissolved through transformation to a water-rich micellar phase.

Anesthetics, Local↗

PubMed2001

A receptor-based biosensor for lipoprotein docking at the endothelial surface and vascular matrix.

Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques showing that HDL has a high binding affinity to the receptor and a protective effect on interfacial heparan sulfate proteoglycan layers, with respect to LDL and Ca(2+) complexation. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca(2+), thus creating the complex formation "proteoglycan-low density lipoprotein-calcium". This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. On the other hand, HDL bound to heparan sulfate proteoglycan protected against LDL docking and completely suppressed calcification of the proteoglycan-lipoprotein complex. In addition, HDL and aqueous garlic extract were able to reduce the ternary complex deposition and to disintegrate HS-PG/LDL/Ca(2+) aggregates. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a "nanoscopic" level under close to physiological conditions. In particular, Ca(2+)-promoted LDL deposition and the protective effect of HDL, even at high Ca(2+) and LDL concentrations, agree well with previous clinical observations regarding risk and beneficial factors for early stages of atherosclerosis. Therefore, we believe that the system can be of some use in investigations, e.g. of the interplay between different lipoproteins in arteriosclerotic plaque formation, as well as in high throughput screening of candidate drugs to atherosclerosis in a biosensor application.

Arteriosclerosis↗

PubMed2001

Proteolytic degradation of oral biofilms in vitro and in vivo: potential of proteases originating from Euphausia superba for plaque control.

This paper deals with enzymatic removal of dental plaque, in vitro as well as in vivo, using proteases from the Antarctic krill shrimp (Euphausia superba), referred to as Krillase. Krillase exhibits both endo- and exopeptidase activity but has no microbicidal effect. In model systems with pure cultures of oral microorganisms. Krillase demonstrated inhibition of microbial adhesion to saliva-coated hydroxyapatite. Furthermore, a protocol for the growth of reproducible in vitro plaque films has been developed, and effects of Krillase on the plaque film were investigated by means of scanning electron microscopy (SEM). The results showed that Krillase efficiently released microorganisms from plaque in vitro, the effect being dependent on the enzymatic activity. The surface energy of the substratum had a minor influence on the formation and removal of plaque in vitro. Ellipsometric studies on the formation and enzymatic removal of a salivary pellicle indicated that the enzymatic effect on plaque may partly depend on degradation of the salivary pellicle. Krillase was also able to remove plaque accumulated on dentures in vivo. Our results demonstrate the potential of Krillase for plaque control, and that these enzymes are worthy of further investigations including clinical studies and work to find a suitable vehicle.

Actinomyces↗

PubMed2000

Micellization and gelation in block copolymer systems containing local anesthetics.

A formulation consisting of a eutectic mixture of lidocaine and prilocaine, Lutrol((R)) F68 and Lutrol((R)) F127, suitable for anesthetizing the periodontal pocket has previously been developed. This consists of discrete micelles with a diameter of 20-30 nm and has a suitable gelation temperature, a good release profile and excellent long-term stability. In this study, the unimer/micelle transition and gel formation of the formulation, in its concentrated state, are investigated using differential scanning calorimetry (DSC), dye solubilization, rheology, and nuclear magnetic resonance (NMR) self-diffusion. The critical micellization temperature (cmt) and gelation temperature are found to be interconnected and influenced by cosolutes, such as electrolytes and hydrophobic substances, the latter as found particularly for the eutectic mixture of the local anesthetic agents lidocaine and prilocaine. Both cmt and the gelation temperature decrease with increasing pH of the system, i.e. at reduced solubility of the active ingredients. Moreover, both cmt and the gelation temperature increase upon diluting the system with water. The ratio between the two block copolymers present in the system also has an impact on both cmt and the gelation temperature, resulting in a decrease in onset temperature of both processes with an increase of Lutrol((R)) F127. The amount of the active ingredients present in the micelle phase depends on the pH of the system being approximately 0% w/w at pH 5, 50-60% w/w at pH 7.8 and 80% w/w at pH 9.

Anesthetics, Local↗

PubMed2000

Interactions between a lipase and charged surfactants--a comparison between bulk and interfaces.

The interaction between a charged surfactant and a lipase has been investigated by several methods. Interactions in aqueous bulk phase was studied by NMR and by microcalorimetry. Surface tension and neutron reflectivity were used for studies at the air-water interface. Interactions at the interface between a hydrophobic solid surface and water was investigated by ellipsometry. The results obtained are as follows. The cationic surfactant, tetradecyltrimethylammonium bromide (iodide in the NMR experiments), showed strong interaction at the air-water and the hydrophobic solid-water interfaces but no clear indication of an interaction in bulk phase was seen. The anionic surfactant showed no interaction with the lipase neither at the interfaces, nor in bulk. The difference in behavior of the system cationic surfactant-lipase in bulk and at the interfaces may be due to the change in enzyme conformation that is known to occur at interfaces between water and an apolar phase.

Calorimetry↗

PubMed2000

Immobilization of trypsin on porous glycidyl methacrylate beads: effects of polymer hydrophilization.

The immobilization of trypsin at porous glycidyl methacrylate (GMA-GDMA) beads was investigated. In particular, the effects of surface modification of the beads through hydrophilic polymers on the amount protein immobilized and on the extent of retained activity after immobilization were adressed. Furthermore, immobilization at unmodified and hydrophilized beads from aqueous solution was compared to that from a water-in-oil microemulsion. It was found that the amount trypsin immobilized at the unmodified GMA-GDMA beads was significantly higher than that at hydrophilized GMA-GDMA beads. However, also the extent of specific activity loss after immobilization was larger for the unmodified than for the hydrophilized beads. Despite the latter, however, the total activity displayed by the hydrophilized beads was comparable to the unmodified beads at best. On the other hand, by peforming the immobilization from the microemulsion a high immobilization yield can be reached even for the hydrophilized beads, which also results in a higher degree of retained activity in the latter case than obtained for immobilization at the unmodified beads. Using this approach therefore resulted in the highest total activity of the trypsin-activated GMA-GDMA beads.

Journal Article↗

PubMed2000

Nonionic Cellulose Ethers as Potential Drug Delivery Systems for Periodontal Anesthesia.

Nonionic cellulose ethers displaying a lower consolute temperature, or cloud-point, close to body temperature were investigated as potential carrier systems for the delivery of local anesthetic agents to the periodontal pocket. The interaction between the polymers, i.e., ethyl(hydroxyethyl)cellulose (EHEC) and hydrophobically modified EHEC (HM-EHEC), and ionic surfactants was determined in the absence and in the presence of the local anesthetic agents lidocaine and prilocaine. The cloud-point and rheology data indicate interactions between the polymer and both anionic and cationic surfactants. More precisely, a number of ionic surfactants were found to result in an increase in cloud-point at higher surfactant concentrations, a surfactant-concentration-dependent thickening, and a temperature-induced gelation upon heating. Upon addition of the local anesthetic agents lidocaine and prilocaine in their uncharged form to EHEC and HM-EHEC, in the absence of surfactants, only minor interaction with the polymer could be inferred. However, these substances were found to affect the polymer-surfactant interaction. In particular, the drug release rate in vitro as well as the stability and temperature-dependent viscosity were followed for an EHEC/SDS system and EHEC/myristoylcholine bromide system upon addition of lidocaine and prilocaine. The data indicate a possibility of formulating a local anesthetic drug delivery system suitable for administration into the periodontal pocket where at least small amounts of active ingredients can be incorporated into the system without severely affecting the gelation behavior. The results found for the cationic myristoylcholine bromide system are particularly interesting for the application in focus here since this surfactant is antibacterial and readily biodegradable. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Adsorption of Diblock Copolymers of Poly(ethylene oxide) and Poly(lactide) at Hydrophilic Silica from Aqueous Solution.

The adsorption of a series of amphiphilic poly(ethylene oxide)-poly(DL-lactide) (PEO-PL) diblock copolymers at the water/silica interface was investigated by ellipsometry and reflectometry. For all copolymers, a much higher saturation adsorption is found compared to that of the PEO homopolymers, indicating the importance of the PL block for the adsorption. The copolymers display a saturation adsorption that increases with increasing hydrophobic content of the polymer, and decreases with increasing hydrophilic content of the polymer. Despite this, however, the layer thickness observed is rather similar for all polymers, regardless of the length and composition of the copolymers. Moreover, the layer thicknesses were significantly higher than what would be expected for the unperturbered copolymer dimensions. The initial adsorption kinetics of the different copolymers are comparable. The initial adsorption rate increases cooperatively with concentration and is slower than that expected for diffusion-controlled adsorption. Moreover, the adsorption increases only slightly over a concentration the range from 20 to 50 degrees C. Furthermore, pH titrations show that all polymers exhibit a critical desorption pH of 8-9, which is lower than the corresponding value of pH 10.5 observed for the PEO homopolymer. These results are discussed in terms of the adsorption mechanism and the adsorbed layer structure and formation. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Adsorption of Diblock Copolymers of Poly(ethylene oxide) and Polylactide at Hydrophobized Silica from Aqueous Solution.

The adsorption of a series of amphiphilic diblock copolymers of poly(ethylene oxide) (PEO) and poly(DL-lactide) (PL) at hydrophobized silica from aqueous solution was studied using time-resolved ellipsometry and reflectometry. The adsorbed amounts only display a weak dependence on the copolymer composition in both water and phosphate-buffered solution. For the short copolymers, the layer thickness decreases slightly with increasing length of the hydrophobic block. Furthermore, in comparison with the short copolymers, the layer thickness of the long copolymers is substantially higher. Upon degradation of the PL block, the adsorbed amount is found to decrease and approach that of the corresponding PEO homopolymer. Protein rejection studies indicate that the adsorption of fibrinogen is inhibited by copolymer preadsorption. The protein rejection is enhanced with increasing surface coverage of the preadsorbed copolymer, but largely independent of the length of the PL block and the PEO block. For all polymers investigated, essentially complete protein rejection is obtained above a critical surface coverage that is significantly lower than the saturation coverage of the copolymers. Removing the copolymer from bulk solution after preadsorption causes a partial desorption, resulting in reduced protein rejection. However, the protein rejection capacity with and without copolymer in the bulk solution is found to be similar at a given surface coverage. Contrary to the behavior of the intact copolymers, fibrinogen adsorption is found to be significant at surfaces pretreated with an extensively degraded copolymer and, in fact, quantitatively comparable to that at the hydrophobic surface in the absence of preadsorption. This finding, together with that of the effect of the copolymer composition on protein rejection, suggests that an efficient protein rejection is maintained until only a few L units remain in the copolymer, i.e., until nearly completed degradation. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

An Aqueous Polymer Two-Phase System as Carrier in the Spray-Drying of Biological Material.

This investigation describes a novel concept in the formulation of carrier systems for the spray-drying of biological materials. As carrier material a system composed of poly(vinyl pyrrolidone) (PVP) and dextran was used. This system yields an aqueous two-phase system in which each phase is enriched in one of the polymers. By varying the composition of the system, the effective structure of a "stirred" system can be varied, covering the entire range from dextran continuous to PVP continuous. This facilitates encapsulation of either of these polymers in a spray-drying operation. In an attempt to investigate the spray-drying from such a system, the surface composition of the spray-dried powder obtained from various compositions of the two-phase system was analyzed by electron spectroscopy for chemical analysis (ESCA), providing information on the distribution of the polymers in the powder and thus also in the spray droplets. The two-phase system was applied for the spray-drying of live bacteria. The survival rate of the bacteria depended on the composition of the two-phase system. The storage stability of the bacteria in these formulations was investigated after storage at room temperature under dry conditions for 4 weeks, and it was found that the survival rate was 10-45%. The results therefore show that this type of formulation holds promise for future applications for micro-organisms as well as other sensitive biological materials such as proteins. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Ellipsometry Studies of Lipoprotein Adsorption.

The adsorption of a number of lipoproteins, i.e., low-density lipoprotein (LDL), oxidized LDL (oxLDL), high-density lipoprotein (HDL), and lipoprotein (a), at silica and methylated silica as well as at the latter surface modified through adsorption of proteoheparan sulfate, was investigated with in situ ellipsometry at close to physiological conditions. It was found that LDL, oxLDL, HDL, and lipoprotein (a) all adsorbed more extensively at silica than at methylated silica. Upon exposure of the methylated silica surface to proteoheparan sulfate, this proteoglycan adsorbs through its hydrophobic moiety, thereby forming a layer similar to that in the biological system, with the polysaccharide chains forming brushes oriented toward the aqueous solution. Analogous to the biological system, both lipoprotein (a) and LDL were found to deposit at such surfaces, the latter particularly in the simultaneous presence of Ca(2+). After HDL pre-exposure, however, no LDL deposition was observed, even at high LDL and Ca(2+) concentrations. These findings correlate well with those obtained from clinical investigations on risk factors for atherosclerosis. Copyright 2000 Academic Press.

Journal Article↗

PubMed2000

Thermosetting microemulsions and mixed micellar solutions as drug delivery systems for periodontal anesthesia.

In the present study, thermosetting microemulsions and mixed micellar solutions were investigated as drug delivery systems for anesthetizing the periodontal pocket. The structure of the systems, consisting of the active ingredients lidocaine and prilocaine, as well as two block copolymers (Lutrol F127 and Lutrol F68), was investigated by NMR spectroscopy and photon correlation spectroscopy (PCS). The results obtained for dilute (1-3% w/w) solutions show discrete micelles with a diameter of 20-30 nm and a critical micellization temperature of 25-35 degrees C. Gel permeation chromatography (GPC) was used to study the distribution of the active ingredients, and indicates a preferential solubilization of the active components in micelles over unimers. Analogous to the Lutrol F127 single component system these formulations display an abrupt gelation on increasing temperature. The gelation temperature was found to depend on both the drug ionization and concentration. These systems have several advantages over emulsion-based formulations including good stability, ease of preparation, increased drug release rate, and improved handling due to the transparency of the formulations.

Anesthesia, Dental↗