Hydrophilic copolymers, protein adsorption

Many kinds of nonbiodegradable vinyl-type hydrophilic polymers were also used in combination with aliphatic polyesters to prepare amphiphilic block copolymers. Two typical examples of the vinyl-polymers used are poly(/V-isopropylacrylamide) (PNIPAAm) [149-152] and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) [153]. PNIPAAm is well known as a temperature-responsive polymer and has been used in biomedicine to provide smart materials. Temperature-responsive nanoparticles or polymer micelles could be prepared using PNIPAAm-6-PLA block copolymers [149-152]. PMPC is also a well-known biocompatible polymer that suppresses protein adsorption and platelet adhesion, and has been used as the hydrophilic outer shell of polymer micelles consisting of a block copolymer of PMPC -co-PLA [153]. Many other vinyl-type polymers used for PLA-based amphiphilic block copolymers were also introduced in a recent review [16]. 

Lens hazing and protein deposition are common problems for wearers of soft contact lenses. Previous experiments with hydrophobic-hydrophilic copolymers exposed to plasma showed protein adsorption to be minimal at intermediate copolymer compositions. Adsorption of proteins from artificial tear solutions to a series of polymers and copolymers ranging in composition from 100% poly (methyl methacrylate) (PMMA) to 100% poly(2-hydroxyethyl methacrylate) (PH EM A) was measured. The total protein adsorption due to the three major proteins in tear fluid (lysozyme, albumin, and immunoglobulins) was at a minimum value at copolymer compositions containing 50% or less PH EM A. The elution of the adsorbed proteins from these polymers and copolymers with various solutions also was investigated to assess the binding mechanism. 

Recent experiments indicate that polymers that contain a balance of hydrophobic (nonpolar) and hydrophilic (polar) chemical groups show minimal protein adsorption and cell adhesion (6). With the intent of rationally designing a contact lens material that would minimize protein adsorption, the adsorption of lysozyme, albumin, and immunoglobulin G (IgG) to a series of hydrophobic and hydrophilic polymers and copolymers was measured. The polymers ranged from 100% poly(methyl methacrylate) (PMMA) to 100% poly(2-hydroxyethyl methacrylate) (PHEMA). Adsorption varied significantly for each protein, as did the elutability of the proteins from the surfaces. 

Figure 2 shows that similar adsorption phenomena are exhibited by lysozyme and albumin. Related work seems to suggest that polymers that contain a certain balance of hydrophobic and hydrophilic chemical groups show minimized biological interaction (for example, low protein adsorption, low thrombus deposition, and low platelet consumption) (6). The adsorption of radiolabeled IgG, however, was maximal at intermediate copolymers. This result has a number of implications with respect to both the fundamental adsorption mechanism and the biocompatibility of these materials. 

The accumulation of proteins on contact lenses has long been viewed as an undesirable event. In this study, the effect of polymer composition on both the total amount of protein on the materials, and on the specific proteins on each polymer composition was documented. The importance of these factors for biological response is not known, so this situation remains a fertile area for investigation. This study also demonstrated that a linear variation in material composition will not necessarily result in a linear variation in absorbed layer protein composition. The minima and maxima noted at intermediate copolymer compositions have strong implications for both understanding the mechanism of protein adsorption and for biological response. Investigation is underway to explore further protein interaction with hydrophobic-hydrophilic copolymer materials. 

Conticello and colleagues have studied the potential of amphiphilic diblock (AB) and triblock (ABA) elastin-like copolymers, where A is a hydrophilic and B a hydrophobic block, to reversibly self-assemble into well-defined micellar aggregates (20,30). Collapse of the hydrophobic block above Tt results in the formation of elastin-based nanoparticles. To provide diversity in the mechanical properties of the micellar structures, the amino acid sequence of the hydrophobic block was varied between plastic (VPAVG) and elastomeric (VPGVG) in nature. The hydrophilic block is designed to maintain solubility and form a protective core that prevents protein adsorption and clearance by the reticuloendothelial system. 

Strategy A was later applied for tailoring the surface of cyclic olefin copolymer (COC), a transparent polymer of high technological importance. Microfluidic chips made from COC were modified with hydrophilic poly[poly(ethylene glycol) methacrylate] grafts, which allowed to reduce nonspecific protein adsorption substantially [15]. 

Despite typically including PEG as a hydrophilic block for the reduction of protein adsorption, the stabiUly of block copolymer micelles can be affected by proteins, even under well-controlled in vitro conditions. Toncheva et al. found that the stability of PEG-6-poly(ortho ester)-6-PEG micelles in presence of bovine serum albumin depended most on the length of the PEG blocks (Toncheva et al. 2003). A study by Liu et al. found that bovine serum albumin did not affect the stability of PEG-i-poly(5-benzyloxytrimethylene carbonate) micelles, but the dmg release was accelerated in the presence of protein (Liu et al. 2005). 

Surface modification with hydrophilic polymers, such as poly(ethylene oxide) (PEO), has been beneficial in improving the blo( compatibility of polymeric biomaterials. Surface-bound PEO is expected to prevent plasma protein adsoiption, platelet adhesion, and bacterial adhesion by the steric repulsion mechanism. PEO-rich surfaces have been prepared either by physical adsorption, or by covalent grafting to the surface. Physically adsorbed PEO homopolymers and copolymers are not very effective since they can be easily displaced from the surface by plasma proteins and cells. Covalent grafting, on the other hand, provides a permanent layer of PEO on the surface. Various methods of PEO grafting to the surface and their effect on plasma protein adsorption, platelet adhesion, and bacterial adhesion is discussed. 

To get some control over protein adsorption, one has to understand the protein-surface interactions in advance. To this end, adsorption isotherms have been obtained for a wide variety of surfaces, from hydrophilic to hydrophobic. Techniques for controlling the surface wettability include varying the terminating groups of SAMs or the ratio of monomers in copolymers. The effects on protein adsorption of factors such as liquid polarity, temperature, pH, solute t)q)e (e.g., electrolyte), and solute concentration have been widely studied [4]. 

Little albumin and y-globulins were adsorbed on the MPC copolymer surface treated with DPPC, which is in sharp contrast to the fact that on a poly(BMA) surface, pretreatment with DPPC was not effective for suppression of protein adsorption (74). The difference in protein adsorption on these polymer surfaces reflects the difference in the orientation of the DPPC which covered the polymer surface. In Fig. 3, the adsorbed amounts of phospholipids, phosphatidylcholine (PC) on the polymers from human plasma is indicated (77). The amount of phospholipids adsorbed on hydrophobic poly(BMA) was almost the same as that on hydrophilic poly(HEMA). On poly(MPC-c< -BMA), a larger amount of phospholipids was adsorbed compared with poly(BMA), and the amount adsorbed increased with an increase in the MPC mole fraction of the copolymer. 

Ishihara et al. also investigated that polysulfone/MFC polymers blend membranes could improve blood compatibility and reduce protein adsorption and platelet adhesion [104-108]. Based on these results, the addition of the MFC polymer to the polysulfone should be a very useful method to improve the functions and blood compatibility. Ultrafiltration antifouling membranes were successfully prepared blending polyethersulfone with 2-methac-ryloyloxyethylphosphorylcholine (MFC) and n-butyl methacrylate (BMA) copolymer, by phase inversion method. IDue to the high hydrophilicity and electric neutrality of MFC-BMA copolymer, the... 

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