Human Plasma Protein Adsorption Research Articles

Profiling of time-dependent human plasma protein adsorption on non-coated and heparin-coated oxygenator membranes.

Patients with severe lung diseases are highly dependent on lung support systems. Despite many improvements, long-term use is not possible, mainly because of the strong body defence reactions (e.g. coagulation, complement system, inflammation and cell activation). The systematic characterization of adsorbed proteins on the gas exchange membrane of the lung system over time can provide insights into the course of various defence reactions and identify possible targets for surface modifications. Using comprehensive mass spectrometry analyses of desorbed proteins, we were able to identify for the first time binding profiles of over 500 proteins over a period of six hours on non-coated and heparin-coated PMP hollow fiber membranes. We observed a higher degree of remodeling of the protein layer on the non-coated membrane than on the coated membrane. In general, there was a higher protein binding on the coated membrane with exception of proteins with a heparin-binding site. Focusing on the most important pathways showed that almost all coagulation factors bound in higher amounts to the non-coated membranes. Furthermore, we could show that the initiator proteins of the complement system bound stronger to the heparinized membranes, but the subsequently activated proteins bound stronger to the non-coated membranes, thus complement activation on heparinized surfaces is mainly due to the alternative complement pathway. Our results provide a comprehensive insight into plasma protein adsorption on oxygenator membranes over time and point to new ways to better understand the processes on the membranes and to develop new specific surface modifications.

Investigation of interaction between MXene nanosheets and human plasma and protein corona composition.

The composition of protein corona affects the behavior and fate of nanoparticles in biological systems, which strongly relates to the intrinsic properties of nanoparticles and proteins. Here, three types of MXene Ti3C2Tx nanosheets are prepared by different etching methods, and certain physicochemical characteristics of the nanosheets before and after exposure to human plasma (HP) are characterized. The Ti3C2Tx nanosheets with protein coronas suffer more easily from aggregation than pristine Ti3C2Tx. The composition of protein coronas by LC-MS/MS-based label-free proteomic analysis reveals a high overlap of protein types and functions but a significant difference in relative protein abundance for the three Ti3C2Tx. Immunoglobulins and coagulation proteins are highly enriched while albumin is depleted in the coronas compared with their abundance in original HP. The random forest classification model predicts that the main driving forces for the adsorption of HP proteins on Ti3C2Tx are hydrogen bonding, steric hindrance, and hydrophobic interaction. This study provides insights into the colloidal stability of Ti3C2Tx nanosheets and their interaction with human plasma proteins.

Human plasma protein adsorption to elastinlike polypeptide nanoparticles.

Elastin-like polypeptides (ELPs) are being developed for numerous biomedical applications. There is a limited understanding of ELP biocompatibility, with conflicting results in the literature. Protein adsorption is the fate determining event for blood-contacting biomaterials. The aim of this study is to elucidate the biocompatibility of ELP-based nanoparticles by examining the adsorbed proteome from platelet poor human plasma as a function of the physicochemical properties of these nanoparticles: diameter, amino acid hydrophobicity, and chain length. It was found that all ELP constructs had adsorbed an extremely large amount of albumin and high levels of immunoglobulin G and activated complement factor 3. Variations in the compositions of the proteomes across the eight nanoparticle systems studied were observed for plasminogen, fibronectin, activated fibrinogen, and coagulation modulating antithrombin and alpha2 macroglobulin. Plasma clotting experiments showed that ELP-based nanoparticles slightly inhibited normal blood clotting, with shorter and/or more hydrophilic constructs showing a greater difference from the control than longer or more hydrophobic constructs. These results indicate that ELP nanoparticles, regardless of chain length, particle diameter, or amino acid hydrophobicity, may have the potential to stimulate a humoral immune response via immunoglobulin G and activated complement factor 3 despite the large amounts of albumin adsorbed at the blood-material interface.

Functionalization of alkyne-terminated thermally hydrocarbonized porous silicon nanoparticles with targeting peptides and antifouling polymers: effect on the human plasma protein adsorption.

Porous silicon (PSi) nanomaterials combine a high drug loading capacity and tunable surface chemistry with various surface modifications to meet the requirements for biomedical applications. In this work, alkyne-terminated thermally hydrocarbonized porous silicon (THCPSi) nanoparticles were fabricated and postmodified using five bioactive molecules (targeting peptides and antifouling polymers) via a single-step click chemistry to modulate the bioactivity of the THCPSi nanoparticles, such as enhancing the cellular uptake and reducing the plasma protein association. The size of the nanoparticles after modification was increased from 176 to 180-220 nm. Dextran 40 kDa modified THCPSi nanoparticles showed the highest stability in aqueous buffer. Both peptide- and polymer-functionalized THCPSi nanoparticles showed an extensive cellular uptake which was dependent on the functionalized moieties presented on the surface of the nanoparticles. The plasma protein adsorption study showed that the surface modification with different peptides or polymers induced different protein association profiles. Dextran 40 kDa functionalized THCPSi nanoparticles presented the least protein association. Overall, these results demonstrate that the "click" conjugation of the biomolecules onto the alkyne-terminated THCPSi nanoparticles is a versatile and simple approach to modulate the surface chemistry, which has high potential for biomedical applications.

Immobilization of superoxide dismutase/catalase onto polysulfone membranes to suppress hemodialysis-induced oxidative stress: A comparison of two immobilization methods

The objective of this study is to improve the blood compatibility of polysulfone (PSF) based hemodialysis membranes through generating antioxidative surfaces with superoxide dismutase (SOD)/catalase (CAT) enzyme couple immobilization. Enzymes were attached both covalently and ionically on the plasma treated and polyethyleneimine (PEI) deposited membranes, respectively. The loss of enzymes from PEI modified surface at the end of 4h was found to be relatively higher during storage in phosphate buffered saline (PBS) at pH 7.4 when compared to the enzymes on the plasma treated surface. The kinetic studies indicated that SOD catalyzed the reaction in the diffusion-limited regime at all substrate concentrations and its inactivation by hydrogen peroxide was prevented in the presence of CAT. SOD/CAT coated PSF membranes were capable of reducing the levels of reactive oxygen species in blood and can significantly prolong activated partial thromboplastin time. In addition, both the adsorption of human plasma proteins and platelet activation on all modified membranes decreased significantly compared to the unmodified PSF membranes. Proposed modification methods did not affect high permeability, high mechanical strength or the non-toxic properties of the PSF membranes.

Retraction Note: Plasma protein adsorption to zwitterionic poly (carboxybetaine methacrylate) modified surfaces: chain chemistry and end-group effects on protein adsorption kinetics, adsorbed amounts and immunoblots

Protein–surface interactions are crucial to the overall biocompatability of biomaterials, and are thought to be the impetus towards the adverse host responses such as blood coagulation and complement activation. Only a few studies hint at the ultra-low fouling potential of zwitterionic poly(carboxybetaine methacrylate) (PCBMA) grafted surfaces and, of those, very few systematically investigate their non-fouling behavior. In this work, single protein adsorption studies as well as protein adsorption from complex solutions (i.e. human plasma) were used to evaluate the non-fouling potential of PCBMA grafted silica wafers prepared by nitroxide-mediated free radical polymerization. PCBMAs used for surface grafting varied in charge separating spacer groups that influence the overall surface charges, and chain end-groups that influence the overall hydrophilicity, thereby, allows a better understanding of these effects towards the protein adsorption for these materials. In situ ellipsometry was used to quantify the adsorbed layer thickness and adsorption kinetics for the adsorption of four proteins from single protein buffer solutions, viz, lysozyme, α-lactalbumin, human serum albumin and fibrinogen. Total amount of protein adsorbed on surfaces differed as a function of surface properties and protein characteristics. Finally, immunoblots results showed that human plasma protein adsorption to these surfaces resulted, primarily, in the adsorption of human serum albumin, with total protein adsorbed amounts being the lowest for PCBMA-3 (TEMPO). It was apparent that surface charge and chain hydrophilicity directly influenced protein adsorption behavior of PCBMA systems and are promising materials for biomedical applications.

Effect of DOPE and cholesterol on the protein adsorption onto lipid nanoparticles

Upon administration, nanoparticles (NPs) are exposed to biological fluids from which they adsorb proteins and other biomolecules to form a “protein corona”. NP–protein interactions are still poorly understood and quantitative studies to characterize them remain scarce. Here, we have investigated the effect of neutral dioleoylphosphatidylethanolamine (DOPE) and cholesterol on the adsorption of human plasma proteins onto the surface of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)-based cationic liposomes of 100 nm in diameter. Quantitative analysis of the protein corona revealed that replacing cationic DOTAP lipids with neutral lipids, being indifferently DOPE or cholesterol, reduces the affinity of fibrinogen, prothrombin, vitamin K, and vitronectin for the lipid surface. On the other side, DOPE specifically promotes the adsorption of apolipoproteins and serum albumin, while cholesterol induces the preferential binding of immunoglobulins and complement proteins. The results of this study will help to explain why NPs of different lipid compositions have a dramatic difference in their in vivo transfection efficiency and will be useful for design of lipid NPs with optimal circulation profiles.

Surface modification of polysulfone based hemodialysis membranes with layer by layer self assembly of polyethyleneimine/alginate-heparin: a simple polyelectrolyte blend approach for heparin immobilization

This study intends to improve blood compatibility of polysulfone (PSF) membranes by generating a nonthrombogenic surface through heparin immobilization. To achieve this task, the support membrane prepared from a blend of PSF and sulfonated polysulfone (SPSF) was modified with layer by layer (LBL) deposition of polyethyleneimine (PEI) and alginate (ALG) and heparin blended with ALG was immobilized only on the outermost surface of the LBL assembly. The results have shown that the adsorption of human plasma proteins and platelet activation on the LBL modified membranes decreased significantly compared with the unmodified PSF and PSF-SPSF blend membranes. Furthermore, blending ALG with a small amount of heparin remarkably prolonged the APTT values of heparin free PEI/ALG coated membranes. It is envisaged that the use of a blend of HEP and ALG only in the terminating layer of the LBL assembly can be an economical and alternative modification technique to create nonthrombogenic surfaces.

RETRACTED ARTICLE: Plasma Protein Adsorption to Zwitterionic Poly (Carboxybetaine Methacrylate) Modified Surfaces: Chain Chemistry and End-Group Effects on Protein Adsorption Kinetics, Adsorbed Amounts and Immunoblots

Protein-surface interactions are crucial to the overall biocompatability of biomaterials, and are thought to be the impetus towards the adverse host responses such as blood coagulation and complement activation. Only a few studies hint at the ultra-low fouling potential of zwitterionic poly(carboxybetaine methacrylate) (PCBMA) grafted surfaces and, of those, very few systematically investigate their non-fouling behavior. In this work, single protein adsorption studies as well as protein adsorption from complex solutions (i.e. human plasma) were used to evaluate the non-fouling potential of PCBMA grafted silica wafers prepared by nitroxide-mediated free radical polymerization. PCBMAs used for surface grafting varied in charge separating spacer groups that influence the overall surface charges, and chain end-groups that influence the overall hydrophilicity, thereby, allows a better understanding of these effects towards the protein adsorption for these materials. In situ ellipsometry was used to quantify the adsorbed layer thickness and adsorption kinetics for the adsorption of four proteins from single protein buffer solutions, viz, lysozyme, α-lactalbumin, human serum albumin and fibrinogen. Total amount of protein adsorbed on surfaces differed as a function of surface properties and protein characteristics. Finally, immunoblots results showed that human plasma protein adsorption to these surfaces resulted, primarily, in the adsorption of human serum albumin, with total protein adsorbed amounts being the lowest for PCBMA-3 (TEMPO). It was apparent that surface charge and chain hydrophilicity directly influenced protein adsorption behavior of PCBMA systems and are promising materials for biomedical applications.

Mechanisms of human plasma protein adsorption on the surface of perfluorocarbon emulsion stabilized with proxanol 268

It has been shown that sorption of most proteins with the molecular weight lower than 200 kDa from human blood plasma on the surface of perfluorocarbon emulsion, stabilized with proxanol 268, is mainly based on hydrophobic interaction, whereas sorption of immunoglobulin G is mainly the result of electrostatic interaction. The removal of lipidic components from plasma leads to the increase of a total amount of adsorbed proteins by 35%. Particularly, when lipidic components are removed, sorption of apolipoprotein AI and immunoglobulin G is considerably bettered as well as sorption of other proteins with the molecular weight of about 50 and 60 kDa occurs. It has been out that apolipoprotein AI in the adsorbed condition loses its capability of tryptophan fluorescence, which might be probably determined by the quenching influence of the perfluorocarbon core of nanoparticle. We think that the findings obtained also indicates considerable conformational rearrangements of this protein during adsorption. It was shown, that the fluorescence of proteins with sorption on nanoparticles in emulsion based on the hydrophobic interaction, is completely or partially quenched.

Vitamin E modifies poly(D,L)lactic acid wettability and reduces bacterial adhesion

Highly biocompatible polylactic acid (PLA)-derived polymers are used for different biomedical applications such as orthopaedic screws and drug delivery devices. Nevertheless their clinical use is limited by their proinflammatory characteristics. Vitamin E (α-tocopherol, Vit. E), a natural antioxidant and anti-inflammatory agent has been used to improve different biomaterials biostability [1], and among them also P(D,L)LA [2]. In this work, addition of Vit.E (10-40% w/v) to P(D,L)LA films obtained by solvent casting technique increased polymer surface wettability and human plasma protein adsorption, while addition of Vit.E acetate (Vit.E Ac, 10-40% w/v), the acetic ester of α-tocopherol, often used as an alternative to Vit.E itself, failed in modifying polymer wettability. On the other hand, bacterial adhesion experiments onto control, Vit.E and Vit.E Ac enriched P(D,L)LA films showed that both presence of Vit.E and Vit.E Ac was able to reduce the adhesion of the RP62A Staphylococcus epidermidis strain [3]. In particular, in PLA + Vit. E samples the decrease in bacterial adhesion was of 56%, while, in the case of PLA + Vit. E Ac samples the decrease was of 40%. These preliminary data suggest that Vit. E addition to PLA containing medical devices could improve their resistance to bacterial infections.

DNA affects the composition of lipoplex protein corona: A proteomics approach

The distribution of drug delivery systems into the body is affected by plasma proteins adsorbed onto their surface. Furthermore, an exact understanding of the structure and morphology of drug carriers is fundamental to understand their role as gene delivery systems. In this work, the adsorption of human plasma proteins bound to cationic liposomes and to their relative DNA lipoplexes was compared. A shotgun proteomics approach based on HPLC coupled to high resolution MS was used for an efficient identification of proteins adsorbed onto liposome and lipoplex surfaces. The distinct pattern of proteins adsorbed helps to better understand the DNA compaction process. The experimental evidence leads us to hypothesize that polyanionic DNA is associated to the lipoplex surface and can interact with basic plasma proteins. Such a finding is in agreement with recent results showing that lipoplexes are multilamellar DNA/lipid domains partially decorated with DNA at their surface. Proteomics experiments showed that the lipoplex corona is rich of biologically relevant proteins such as fibronectin, histones and complement proteins. Our results provide novel insights to understand how lipoplexes activate the immune system and why they are rapidly cleared from the blood stream. The differences in the protein adsorption data detected in the presented experiments could be the basis for the establishment of a correlation between protein adsorption pattern and in vivo fate of intravenously administered nanoparticles and will require some consideration in the future.

Hemocompatibility of pyrolytic carbon in comparison with other biomaterials

The present generation of mechanical heart-valves prostheses offers significantly improved blood compatibility, combined with appropriate physical and mechanical properties and durability; however, thromboembolism persists as a crucial clinical complication because of the key role played by adsorbed plasma proteins and adherent platelets in determining hemocompatibility. In the present work human plasma protein adsorption and platelet adhesion and activation were evaluated on four materials, selected according to their different physico-chemical and morphological properties: pyrolytic carbon (PyC), titanium alloy Ti–6Al–4V (Ti), tissue culture polystyrene (TCPS) and polystyrene sterilized by γ -irradiation (StPS). Morphological and chemical properties of surfaces were assessed by Time of Flight Secondary Ion Mass Spectrometry (Tof-SIMS), X-ray Photoemission Spectroscopy (XPS), Atomic Force Microscopy (AFM) and Contact Angle (CA) analysis, while protein adsorption and platelet adhesion and activation were evaluated by colorimetric and immunofluorescence tests and Scanning Electron Microscopy (SEM), respectively. Among the analyzed materials, PyC induced the lowest level of protein adsorption and platelet adhesion and activation. In particular, immunofluorescence analysis of fibronectin (FN), fibrinogen (FG), von Willebrand factor (vWF), Hageman factor (FXII) and albumin (ALB) showed that PyC surface was characterized by high levels of FG adsorption, low levels of FN, ALB and vWF and the absence of FXII. Finally, when analyzing the biological response as a function of surface properties, it was found that protein adhesiveness increased with increasing contact angle values. To the contrary, platelet activation related to the total amount of adherent proteins was poor while cell activation was possibly dependent on the detailed composition of the underlying protein layer. Furthermore, differences in surface roughness of the examined materials did not seem to influence the biological response in terms of platelet activation and protein adsorption.

Human plasma protein adsorption onto dextranized surfaces: A two-dimensional electrophoresis and mass spectrometry study

Protein adsorption is fundamental to thrombosis and to the design of biocompatible materials. We report a two-dimensional electrophoresis and mass spectrometry study to characterize multiple human plasma proteins adsorbed onto four different types of model surfaces: silicon oxide, dextranized silicon, polyurethane and dextranized polyurethane. Dextran was grafted onto the surfaces of silicon and polyurethane to mimic the blood-contacting endothelial cell glycocalyx surface. Surface topography and hydrophobicity/hydrophilicity were determined and analyzed using atomic force microscopy and water contact angle measurements, respectively. Using two-dimensional electrophoresis, we show that, relative to the unmodified surfaces, dextranization significantly inhibits the adsorption of several human plasma proteins including IGHG1 protein, fibrinogen, haptoglobin, Apo A-IV, Apo A-I, immunoglobulin, serum retinal-binding protein and truncated serum albumin. We further demonstrate the selectivity of plasma protein adsorbed onto the different functionalized surfaces and the potential to control and manipulate proteins adsorption on the surfaces of medical devices, implants and microfluidic devices. This result shows that adsorption experiments using a single protein or a binary mixture of proteins are consistent with competitive protein adsorption studies. In summary, these studies indicate that coating blood-contacting biomedical applications with dextran is an effective route to reduce thrombo-inflammatory responses and to surface-direct biological activities.

A systematic SPR study of human plasma protein adsorption behavior on the controlled surface packing of self‐assembled poly(ethylene oxide) triblock copolymer surfaces

A well-controlled biocompatible nonfouling surface is significant for biomedical requirements, especially for the improvement of biocompatibility. We demonstrate the low or nonbiofouling surfaces by coating hydrophobic-hydrophilic triblock copolymers of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) on the CH(3)-terminated self-assembled monolayer (SAM). Two types of copolymers are used to modify the surface, one with different PEO/PPO ratios ( approximately 20/80, 40/60, and 80/20, w/w) but the same PPO molecular weight ( approximately 2 k), the other with different copolymer MWs ( approximately 9, 11, and 15 k) but the same PEO/PPO ratio (80/20, w/w). In situ surface plasmon resonance (SPR) sensor is used to evaluate polymer adsorption on the SAMs and subsequent protein adsorption on the copolymer-treated surface. The effects of PEO-PPO-PEO molecular weight, PPO-to-PEO ratio, and ionic strength on protein adsorption from single protein solutions of fibrinogen, BSA, and complex mixed proteins are systematically investigated. A Pluronic F108 treated surface is highly resistant to nonspecific protein adsorption under the optimized conditions (MW of 15 k and PEO/PPO ratio of 80/20). This work demonstrates that the PEO-PPO-PEO polymer is able to achieve ultra low fouling surface via surface modification by controlling surface packing density of polymers (molecular weight, hydrophobic/hydrophilic ratio, and hydrophilic group coverage).

Effects of Covalent Functionalization on the Biocompatibility Characteristics of Multi-Walled Carbon Nanotubes

We report the effect of chemical modification of multi-walled carbon nanotubes (MWNTs) on their activation of the human serum complement system, as well as the adsorption of human plasma proteins on MWNTs. Four different types of chemically-modified MWNTs were tested for complement activation via the classical and alternative pathways using haemolytic assays. Human plasma protein binding was also tested using an affinity chromatography technique based on carbon nanotube-Sepharose matrix. Covalent functionalization of MWNTs greatly altered the level of activation of the complement system via the classical pathway. For example, MWNTs functionalised with epsilon-caprolactam or L-alanine showed respectively >90% and >75% reduction in classical pathway activation compared with unmodified MWNTs. These results demonstrate for the first time that these types of chemical modification are able to alter considerably the levels of specific complement proteins bound by pristine MWNTs (used as a control experiment). The reduced levels of complement activation via the classical pathway, that are likely to increase biocompatibility, were directly correlated with the amount of C1q protein bound to chemically modified carbon nanotubes. An inverse correlation was also observed between the amount of complement factor H bound to chemically modified MWNTs and the level of complement consumption via the alternative pathway. Binding of human plasma and serum proteins to pristine and modified MWNTs was highly selective. The chemical modifications studied generally increased nanotube dispersibility in aqueous media, but diminished protein adsorption.

Study of Protein Adsorption onto a Polymer Film by in-situ UV Attenuated Total Reflectance Spectroscopy

AbstractOur work presents results on human plasma protein adsorption onto a polyacrylic acid (PAA) film prepared via surface wave plasma (SWP) induced graft polymerization. The PAA film prepared in this manner is characterized by a carboxyl functional group and a constant contact angle in water of 35°. The adsorption kinetics of human plasma fibrinogen (HPF) and human serum albumin (HSA) proteins were measured by in-situ UV-ATR spectroscopy. The free energy of adsorption on PAA treated as well as untreated surfaces was −28 kJ M−1 and −22 kJ M−1 for HPF and HSA, respectively, regardless of surface chemistry. We determined that 14 μM and 6 μM HPF concentrations are enough to cover half of the maximum possible of surface coverage on silica and PAA film, respectively. HSA protein concentrations of 154 μM and 118 μM are enough to cover half of the maximum accessible surface of silica and PAA film, respectively. For surface treatment of implants with PAA polymer and protein, the necessary protein concentration for effective surface coverage should be known.

Adsorption of human plasma proteins to modified titanium surfaces

The aim of this study was to examine the effect of modified titanium (Ti) surfaces on the initial events of plasma proteins adsorption. 'Ti disks' with three types of surface modifications were compared: machined, acid-etched and acid-etched and blasted. Physical and chemical characterizations of the surfaces were performed via scanning electron microscopy (SEM), atomic force microscopy (AFM) used for analysis of surface topography, characterization of the titanium oxide (TiO2) layer was carried out by X-ray photoelectron spectroscopy (XPS) and characterization of surface energy by the determination of contact angles. Evaluation of plasma proteins' adsorption to the treated Ti surfaces was performed by mass spectrometry, confocal laser scanning microscopy and XPS. Quantitative proteins' assessment was carried out by enzyme-linked immunosorbent assay. SEM images revealed major differences in the topography of the examined surfaces. Acid-etched and blasted Ti surfaces were found to have higher roughness values and a thicker TiO2 layer as compared with acid-etched and machined surfaces. Moreover, acid-etched and blasted surfaces showed high surface area differentiation, pointing to a high increase in the three-dimensional (3D) surface area over the 2D surface area compared with the other surfaces. Adsorption of plasma proteins to the acid-etched and blasted Ti surfaces was both qualitatively and quantitatively more intense compared with the machined and acid-etched surfaces. This was shown for each examined protein, total proteins and by the removal degree of the protein coat. The preferential adsorption of plasma proteins to the acid-etched and blasted Ti surfaces may be explained by its topographical characteristics and by the increase of the 3D surface area of this modified surface.

Haemocompatibility of vitamin-E-enriched poly(D,L-lactic acid)

Poly(D,L-lactic acid) (P(D,L)LA) is a biocompatible and biodegradable polymer whose use is limited to orthopaedic applications. In fact, the mechanical properties of P(D,L)LA are not usually utilized for cardiovascular applications, as the polymer has been proven to activate both granulocyte- and platelet-causing inflammation. In order to improve P(D,L)LA haemocompatibility vitamin E (α-tocoferol, 10–30% (w/w)), a natural biological anti-oxidant and anti-inflammatory agent, was added during the solvent casting of P(D,L)LA film. The P(D,L)LA films obtained were then analysed using FT-IR analysis to assess vitamin E presence; polymer surface wettability and human plasma protein adsorption were measured by sessile drop test, spectrophotometric protein quantification and Western blot, respectively, and polymer haemocompatibility was assessed measuring platelet and granulocyte adhesion and whole blood coagulation. Vitamin E presence caused an increase in polymer surface wettability and human plasma protein adsorption. The combination of both effects may account for the decrease in platelet and granulocyte adhesion and for the doubling of whole blood clotting time measured onto vitamin-E-enriched P(D,L)LA compared to control P(D,L)LA. Our results indicate that vitamin E addition improves P(D,L)LA haemocompatibility, making this polymer suitable for cardiovascular application.

Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: Comparison of plasma protein adsorption patterns

Plasma proteins enriched on the surface of drug-delivery-purpose nanoparticles are regarded as key factors for determination of in vivo organ distribution after intravenous injection. Polysorbate 80-coated polybutylcyanoacrylate (PBCA) nanoparticles, preferentially adsorbing apolipoprotein E (apoE) on their surface, have previously been considered to deliver various drugs to the brain. In the present study, in vivo well tolerable solid lipid nanoparticles (SLN) using different types of polysorbates as stabilizers were produced. The influence of the different surfactants on in vitro adsorption of human plasma proteins was investigated using two-dimensional polyacrylamide gel electrophoresis (2-DE). Possible correlations of different amounts of adsorbed apoE to the hydrophilic–lipophilic balance (HLB) of the polysorbates are shown and discussed. Apolipoprotein C-II, albumin and immunoglobulin G, which are also decisive plasma proteins with regard to site-specific drug delivery of intravenously injected carriers to the brain, are compared with regard to adsorption. Moreover, certain similarities to the plasma protein adsorption patterns of previously analysed brain-specific PBCA nanoparticles could be detected. Despite some differences in adsorption behavior of proteins on the surface of polysorbate-stabilized SLN and PBCA nanoparticles, we conclude that in both cases polysorbate 80 might have the highest potential to deliver drugs to the brain.