Surface immobilization of galactose onto aliphatic biodegradable polymers for hepatocyte culture

A novel surface modification method of biodegradable polymers was investigated for inducing the attachment of specific cells onto the polymer surface via ligand-receptor interactions. Galactose, a targeting ligand specific to asialoglycoprotein receptors present on cell membrane of hepatocytes, was introduced on the surface of poly(D,L-lactic-co-glycolic acid) (PLGA) films. A terminal end group of carboxylic acid in PLGA was activated by dicyclohexylcarbodiimide and N-hydroxysuccinimide for the direct conjugation of lactose by reductive amination reaction. Di-block copolymers of PLGA-b-poly(ethylene glycol) (PEG) having a free terminal amine group were also synthesized and used for the conjugation of galactose for the introduction of a PEG spacer between PLGA and galactose. The presence of galactose moieties on the blend film surface was characterized by measuring water contact angle and X-ray photon spectroscopy, and the amount of galactose was indirectly determined by a specific lectin-binding assay. With increasing the galactose concentration on the blend film surface, the initial attachment as well as the cell viability of hepatocyates concomitantly increased. The introduction of PEG spacer reduced the cell attachment and viability. Albumin secretion rate from hepatocytes was enhanced for galactose modified surfaces, whereas it was reduced for the surfaces not having galactose moieties.     

Interaction between proteins and polyphosphazene derivatives having a galactose moiety

For tissue engineering applications, it is necessary to balance the need for specific biological interactions with the need to prevent unfavorable nonspecific interactions. For this purpose, novel poly[(organo)phosphazenes] were synthesized having galactose and/or poly(ethylene glycol) (PEG) side chains. The synthesis was described previously. Here, we investigate the human serum albumin (HSA) adhesion to these polymers using surface plasmon resonance (SPR). We could conclude that the incorporation of PEG reduced the protein adsorption. The influence of the galactose moieties was investigated using SPR and a sugar-lectin binding assay. The interaction between a lectin (Peanut agglutinin, PNA or Ricinus communis-agglutinin, RCA) and the polyphosphazene derivatives was evaluated. Type IIA polymers, having aminohexyl-galactose, phenylalanine ethyl ester, and glycine ethyl ester side chains, were capable of binding with the lectin. As the amount of galactose was increased, the extent of the galactose specific lectin binding was also increased (higher RU or absorbance). PEG containing polymers failed to bind specifically with the lectin. The presence of PEG, either as a spacer or as additional chains, interfered with the establishment of contact between the galactose and the binding site on the lectin. The adsorption of PNA or RCA to these types of polymers was attributed to nonspecific interactions. SPR was also used to determine rate and equilibrium constants. In addition the effect of the addition of water soluble polyphosphazenes on the enzymatic cleavage of o-nitrophenyl-beta-D-galactopyranoside was investigated. The galactose moieties were not available as inhibitors because of the presence of PEG.     

Cell fouling resistance of polymer brushes grafted from ti substrates by surface-initiated polymerization: effect of ethylene glycol side chain length

This paper presents a comparative study on the antifouling properties of poly(ethylene glycol) (PEG)-based polymer coatings prepared by surface-initiated polymerization (SIP). Three types of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMEMA) polymer thin films of approximate 100 nm thickness were grafted from a catechol initiator that was immobilized on a Ti substrate. OEGMEMA monomers containing side chains of 4, 9, and 23 EG units were used in surface-initiated atom transfer radical polymerization (SI-ATRP) to form POEGMEMA-4, -9, and -23 polymer brushes. The chemical composition, thickness, and wettability of the polymer brushes were characterized by X-ray photoelectron spectroscopy (XPS), ellipsometry, and static water contact angle measurements, respectively. The dependence of antifouling performance on EG side chain length was systemically tested and compared by 3T3 fibroblast cell adhesion assays. Results from 4-h cell culture experiments revealed the complete absence of cell attachment on all the grafted Ti substrates. Excellent cell fouling resistance continued with little dependence on EG side chain length up to three weeks, after which long-term antifouling performance depended on the EG chain length as the grafted samples reached confluent cell coverage in 7, 10, and 11 weeks for POEGMEMA-4, -9, and -23, respectively.     

Electrochemical deposition and surface-initiated RAFT polymerization: protein and cell-resistant PPEGMEMA polymer brushes

This paper introduces a novel and versatile method of grafting protein and cell-resistant poly(poly ethylene glycol methyl ether methacrylate) (PPEGMEMA) brushes on conducting Au surface. The process started with the electrochemical deposition and full characterization of an electro-active chain transfer agent (CTA) on the Au surface. The electrochemical behavior of the CTA was investigated by cyclic voltammetry (CV) while the deposition and stability of the CTA on the surface were confirmed by ellipsometry, contact angle, and X-ray photoelectron spectroscopy (XPS). The capability of the electrodeposited CTA to mediate surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization on both the polymethyl methacrylate (PMMA; model polymer) and PPEGMEMA brushes was demonstrated by the increase in thicknesses of the films after polymerization. Contact angles also decreased with the incorporation of the more hydrophilic brushes. Significant changes in the morphologies of the films before and after polymerization were also observed with atomic force microscopy (AFM) analyses. Furthermore, XPS results showed an increase in the O 1s peak intensity relative to C 1s after polymerizations, which confirmed the grafting of polyethyleneglycol (PEG) bearing brushes. The ability of the PPEGMEMA-modified Au surface to resist nonspecific adhesion of proteins and cells was monitored and confirmed by XPS, ellipsometry, contact angle, AFM, and fluorescence imaging. The new method presented has potential application as robust protein and cell-resistant coatings for electrically conducting electrodes and biomedical devices.     

Comparison of coatings from reactive star shaped PEG-stat-PPG prepolymers and grafted linear PEG for biological and medical applications

Grafting of poly(ethylene glycol) (PEG) is a common strategy for reducing nonspecific interactions of surfaces with proteins. We have used grafting at "cloud point" solution conditions that ensures maximum grafting density of linear methoxy terminated PEG-aldehyde (mPEG-ald, M(w) = 5000 and 30000). In an alternative approach, surfaces were modified with layers prepared from isocyanate terminated, star shaped poly(ethylene glycol-stat-propylene glycol) prepolymers (80% ethylene glycol, six arms, M(w) = 3000, 12,000, and 18,000; this compound will be referred to as "Star PEG" in the text). Due to the highly reactive endgroups, these molecules form a dense network on the substrate with a high polymer surface coverage. The two systems were compared regarding their ability to prevent unspecific adsorption of insulin and lysozyme. The layers were analyzed by ellipsometry, contact angle measurements, and XPS. Protein adsorption was monitored by surface MALDI-TOF MS and fluorescence microscopy. No protein adsorption could be detected on Star PEG coatings and on mPEG-ald 5000, whereas mPEG-ald 30,000 could only prevent adsorption of lysozyme but not of the smaller insulin.     

Investigation of the role of hydrophilic chain length in amphiphilic perfluoropolyether/poly(ethylene glycol) networks: towards high-performance antifouling coatings

The facile preparation of amphiphilic network coatings having a hydrophobic dimethacryloxy-functionalized perfluoropolyether (PFPE-DMA; M(w) = 1500 g mol(-1)) crosslinked with hydrophilic monomethacryloxy functionalized poly(ethylene glycol) macromonomers (PEG-MA; M(w) = 300, 475, 1100 g mol(-1)), intended as non-toxic high-performance marine coatings exhibiting antifouling characteristics is demonstrated. The PFPE-DMA was found to be miscible with the PEG-MA. Photo-cured blends of these materials containing 10 wt% of PEG-MA oligomers did not swell significantly in water. PFPE-DMA crosslinked with the highest molecular weight PEG oligomer (ie PEG1100) deterred settlement (attachment) of algal cells and cypris larvae of barnacles compared to a PFPE control coating. Dynamic mechanical analysis of these networks revealed a flexible material. Preferential segregation of the PEG segments at the polymer/air interface resulted in enhanced antifouling performance. The cured amphiphilic PFPE/PEG films showed decreased advancing and receding contact angles with increasing PEG chain length. In particular, the PFPE/PEG1100 network had a much lower advancing contact angle than static contact angle, suggesting that the PEG1100 segments diffuse to the polymer/water interface quickly. The preferential interfacial aggregation of the larger PEG segments enables the coating surface to have a substantially enhanced resistance to settlement of spores of the green seaweed Ulva, cells of the diatom Navicula and cypris larvae of the barnacle Balanus amphitrite as well as low adhesion of sporelings (young plants) of Ulva, adhesion being lower than to a polydimethyl elastomer, Silastic T2.     

Minimization of protein adsorption on poly(vinylidene fluoride)

Surfaces covered with polyethylene glycol (PEG) have been shown to be biocompatible because PEG yields nonimmunogenicity, nonantigenicity and protein rejection. To produce a biocompatible surface coating, we have developed a method for grafting PEG onto modified poly(vinylidene fluoride) (PVDF) films. The first step was to create carboxy groups on the PVDF surface following covalente coupling of polyethylenimine (PEI) to achieve high density of amino groups. These surface amines were reacted with formyl-terminated PEG's with various molecular weight. The modified PVDF surface was characterized by means of static contact angle measurements, infrared (IR) spectroscopy and X-ray photoelectron spectroscopy (XPS). The influence of the chain length on lysozyme repellence was investigated by means of surface-MALDI-Tof mass spectrometry (Surface-MALDI-Tof-MS). Lysozyme adsorption was significantly suppressed on the PEG 5000 modified PVDF surface.     

Synthesis and evaluation of a star amphiphilic block copolymer from poly(epsilon-caprolactone) and poly(ethylene glycol) as a potential drug delivery carrier

A star polymer composed of amphiphilic block copolymer arms has been synthesized and characterized. The core of the star polymer is polyamidoamine (PAMAM) dendrimer, the inner block in the arm is lipophilic poly(epsilon-caprolactone) (PCL), and the outer block in the arm is hydrophilic poly(ethylene glycol) (PEG). The star-PCL polymer was synthesized first by ring-opening polymerization of epsilon-caprolactone with a PAMAM-OH dendrimer as initiator. The PEG polymer was then attached to the PCL terminus by an ester-forming reaction. Characterization with SEC, (1)H NMR, FTIR, TGA, and DSC confirmed the star structure of the polymers. The micelle formation of the star copolymer (star-PCL-PEG) was studied by fluorescence spectroscopy. Hydrophobic dyes and drugs can be encapsulated in the micelles. A loading capacity of up to 22% (w/w) was achieved with etoposide, a hydrophobic anticancer drug. A cytotoxicity assay demonstrated that the star-PCL-PEG copolymer is nontoxic in cell culture. This type of block copolymer can be used as a drug delivery carrier.     

Selective biorecognition and preservation of cell function on carbohydrate-immobilized phosphorylcholine polymers

To obtain synthetic materials capable of selectively recognizing proteins and cells, and preserving their functions, biomembrane mimetic polymers having a phospholipid polar group and carbohydrate side chains were designed. Poly[2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)-co-2-lactobionamidoethyl methacrylate (LAMA)] (PMBL) was synthesized and coated on substrates by solvent evaporation. Selective binding of galactose-recognized lectin, RCA120, to a PMBL surface was investigated by measurement of surface plasmon resonance. The binding of RCA120 to the PMBL surface was confirmed by a remarkable change in resonance angle. The apparent affinity constant of RCA120 to PMBL3.0 (3.0 mol % LAMA unit in the feed) per LAMA unit was 2.77 x 10(5) M(-1). When a glucose-recognized lectin, concanavalin A, was in contact with PMBL, no change in the resonance angle was observed, and any nonspecific fouling of protein on PMBL was effectively reduced. Cells of the human hepatocellular liver carcinoma cell line (HepG2) having asialoglycoprotein receptors (ASGPRs) were seeded on polymer surfaces. On poly(BMA) (PBMA), many adherent cells were observed and were well-spread with monolayer adhesion, but cell adhesion was reduced on poly(MPC-co-BMA) (PMB). HepG2 adhesion was observed on PMBL because the cell has ASGPRs; the number of cells adhering to the PMBL polymer surfaces increased with an increase in the density of galactose residues on the surface. In contrast, adhesion of NIH-3T3 cells to PMBL was reduced in a manner similar to that on PMB because the NIH-3T3 cells did not have ASGPRs. Cell adhesion to the PMBL surface was well-regulated by ligand-receptor interactions. Furthermore, some of the cells adhering to the PMBL surface had a spheroid form, and similarly shaped spheroids were scattered on the surface. Although poly(BMA-co-LAMA) (PBL) has galactose residues, the adherent cells were spread in a manner similar to those on PBMA. The MPC units in PMBL contribute to make a spheroid formation of HepG2 cells. The amount of albumin secreted from a cell was compared with the chemical structure of the substrate. The spheroid shaped cells cultured on the PMBL surface secreted much more albumin than did the spreading cells that adhered to the PBMA. In conclusion, the biomembrane mimetic carbohydrate-immobilized phosphorylcholine polymers produced a suitable surface for biorecognition and preservation of cell function.     

Fluorine-free mixed amphiphilic polymers based on PDMS and PEG side chains for fouling release applications

Fluorine-free mixed amphiphilic block copolymers with mixtures of short side groups of polydimethyl siloxane (PDMS) and polyethylene glycol (PEG) were synthesized and studied for their ability to influence the surface properties and control the adhesion of marine organisms to coated surfaces. The settlement (attachment) and strength of adhesion of two different marine algae, the green seaweed Ulva and the diatom Navicula, were evaluated against the surfaces. It is known that hydrophobic coatings based on polydimethyl siloxane elastomers (PDMSe) are prone to protein adsorption and accumulation of strongly adherent diatom slimes, in contrast to PEG-based hydrophilic surfaces that inhibit protein adsorption and moderate only weak adhesion of diatoms. By incorporating both PDMS and PEG side chains into the polymers, the effect of incorporating both polar and non-polar groups on fouling-release could be studied. The dry surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure spectroscopy (NEXAFS). The ability of these mixed amphiphilic polymers to reconstruct in water was examined using underwater bubble contact angle and dynamic water contact angle experiments. To understand more about surface reconstruction behavior, protein adsorption experiments were carried out with fluorescein isothiocyanate-labeled bovine serum albumin (BSA-FITC) on both dry and pre-soaked surfaces.     

Galactose-substituted alginate 2: conformational aspects

Galactose moieties have been introduced on the uronic groups of alginates from different sources via an N-glycosidic bond, thus affecting the net charge on the polymer chain. The modified polymers have been analyzed by means of viscosity and of high-performance size-exclusion chromatography combined with refractive index multiple angle laser light scattering (HPSEC-RI-MALLS) measurements. The latter technique enabled us to determine the molecular weight of the modified polymers, proving that the synthetic procedure did not affect the chemical integrity of the chain. The intrinsic viscosity and the radius of gyration data showed that the hydrodynamic properties of the polymer chain varied with the degree and the pattern of substitution. In the presence of a relatively low galactose content (up to 19%), a decrease of the hydrodynamic dimensions of the coil was experienced, while on increasing the degree of substitution (especially on GG diads) a re-extension of the chain was discovered. Measurements of intrinsic viscosity at different values of the degree of dissociation have demonstrated that this effect cannot be solely explained by the reduction of the charge density of the polymer. Rather, it implies the occurrence of conformational changes of the chain that are specific to the chemical nature of the site of substitution. These data have been supported by the values of the persistence length of the natural and modified polymers obtained with the Doty-Benoit equation. The chiro-optical properties of the modified polymers studied by means of circular dichroism (CD) spectroscopy confirmed that conformational variations occurred to the polymeric chain upon introduction of galactose residues.     

Fluorine-free mixed amphiphilic polymers based on PDMS and PEG side chains for fouling release applications

Fluorine-free mixed amphiphilic block copolymers with mixtures of short side groups of polydimethyl siloxane (PDMS) and polyethylene glycol (PEG) were synthesized and studied for their ability to influence the surface properties and control the adhesion of marine organisms to coated surfaces. The settlement (attachment) and strength of adhesion of two different marine algae, the green seaweed Ulva and the diatom Navicula, were evaluated against the surfaces. It is known that hydrophobic coatings based on polydimethyl siloxane elastomers (PDMSe) are prone to protein adsorption and accumulation of strongly adherent diatom slimes, in contrast to PEG-based hydrophilic surfaces that inhibit protein adsorption and moderate only weak adhesion of diatoms. By incorporating both PDMS and PEG side chains into the polymers, the effect of incorporating both polar and non-polar groups on fouling-release could be studied. The dry surfaces were characterized by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure spectroscopy (NEXAFS). The ability of these mixed amphiphilic polymers to reconstruct in water was examined using underwater bubble contact angle and dynamic water contact angle experiments. To understand more about surface reconstruction behavior, protein adsorption experiments were carried out with fluorescein isothiocyanate-labeled bovine serum albumin (BSA-FITC) on both dry and pre-soaked surfaces.     

Interaction of poly(ethylene-glycols) with air-water interfaces and lipid monolayers: investigations on surface pressure and surface potential.

We have characterized the surface activity of different-sized poly(ethylene-glycols) (PEG; M(r) 200-100,000 Da) in the presence or absence of lipid monolayers and over a wide range of bulk PEG concentrations (10(-8)-10% w/v). Measurements of the surface potential and surface pressure demonstrate that PEGs interact with the air-water and lipid-water interfaces. Without lipid, PEG added either to the subphase or to the air-water interface forms relatively stable monolayers. Except for very low molecular weight polymers (PEGs < 1000 Da), low concentrations of PEG in the subphase (between 10(-5) and 10(-4)% w/v) increase the surface potential from zero (with respect to the potential of a pure air-water interface) to a plateau value of approximately 440 mV. At much higher polymer concentrations, > 10(-1)% (w/v), depending on the molecular weight of the PEG and corresponding to the concentration at which the polymers in solution are likely to overlap, the surface potential decreases. High concentrations of PEG in the subphase cause a similar decrease in the surface potential of densely packed lipid monolayers spread from either diphytanoyl phosphatidylcholine (DPhPC), dipalmitoyl phosphatidylcholine (DPPC), or dioleoyl phosphatidylserine (DOPS). Adding PEG as a monolayer at the air-water interface also affects the surface activity of DPhPC or DPPC monolayers. At low lipid concentration, the surface pressure and potential are determined by the polymer. For intermediate lipid concentrations, the surface pressure-area and surface potential-area isotherms show that the effects due to lipid and PEG are not always additive and that the polymer's effect is distinct for the two lipids. When PEG-lipid-mixed monolayers are compressed to surface pressures greater than the collapse pressure for a PEG monolayer, the surface pressure-area and surface potential-area isotherms approach that of the lipid alone, suggesting that for this experimental condition PEG is expelled from the interface.     

Azobenzene-modified poly(l-glutamic acid) (AZOPLGA): its conformational and photodynamic properties

Azobenzene-modified poly(l-glutamic acid) (AZOPLGA) polymers with 22 and 35 mol % of azo chromophores in the side chains have been synthesized by condensing 4-methoxy-4'-aminoazobenzene and poly(l-glutamic acid). These polymers have been characterized by NMR, FT-IR, and UV-visible spectroscopic techniques. The conformational features of the polymer backbone chains in the films that were cast from the polymer solutions prepared in different solvents have been investigated by circular dichroism spectroscopy. Experimental data suggested that the thermal cis-trans relaxation and photoinduced birefringence, which are related to the azo chromophores in the side chains of polymer, are not affected by the conformations of polymer backbones. However, the modulations of the surface relief gratings, the result of photoinduced mass transport process, recorded on these polymers are sensitive to polymer main chain conformation, as well as the degree of functionalization.     

Novel monodisperse PEG-dendrons as new tools for targeted drug delivery: synthesis, characterization and cellular uptake

Dendrimers, dendrons, and hyperbranched polymers are gaining popularity as novel drugs, imaging agents, and drug delivery systems. They present advantages of well-defined molecular weight, multivalent surfaces, and high drug carrying capacity. Moreover, it is emerging that such architectures can display unique endocytic properties. As poly(ethylene glycol) (PEG) is widely used for protein and drug conjugation, the aim of this study was for the first time to synthesize novel, branched PEG-based architectures, to define their cytotoxicity and, via preparation of Oregon green (OG) conjugates define the effect of structure on their cellular uptake. Five PEG-based dendrons were synthesized using monodisperse Fmoc-amino PEG propionic acid (M(w) = 840) as a monomer, and cadaverine, tris(2-aminoethyl)amine or lysine as the branching moieties. These were diamino,bisPEG (M(w) = 1300); triamino,trisPEG (Mw = 1946); tetraamino,tetraPEG (M(w) = 3956); monocarboxy,diamino,bisPEG (M(w) = 1346); and monocarboxy,tetraamino,tetraPEG (M(w) = 3999). These products had NH(2) or both NH(2) and COOH terminal groups and the identity was verified by amino group analysis and ESI-TOF mass spectroscopy. Purity was determined by HPLC. Representative structures were not toxic towards an endothelial-like cell line (ECV304) at concentrations up to 4 mg/mL (over 72 h). At 37 degrees C, all of the OG-labeled PEG dendrons showed progressive uptake by ECV304 cells, but tetraamino,tetraPEG showed the greatest rate of internalization over the first 20 min. Cellular uptake was inhibited at 4 degrees C, and PEG dendron localization to perinuclear vesicles was confirmed by fluorescence microscopy. These well-defined novel architectures have potential for further development as targetable drug delivery systems or tools for construction of structurally defined modified surfaces.     

Synthesis of multifunctional chitosan with galactose as a targeting ligand for glycoprotein receptor

Chitosan-O-PEG-galactose was synthesized through hydroxyl groups of chitosan, which followed several steps including protection of amino group of chitosan, pegylation of chitosan, galactosylation of pegylated chitosan, and final removal of protection to obtain chitosan-O-PEG-galactose. The synthesized intermediates and final product were characterized and confirmed by ¹H NMR and FTIR, and the amounts of PEG and galactose conjugated with chitosan were measured. The pegylated chitosan possesses amphiphilic property in terms of soluble in both neutral aqueous (e.g., water) and organic solvents (e.g., DMF, dichloromethane). The corresponding critical micelle concentration is measured to be 0.56 mg/mL, and the size of micelles is 294.5 ± 2.3 nm with polydispersity 0.123 ± 0.021. The contents of PEG and galactose conjugated in chitosan-O-PEG-galactose are 98.09 ± 4.63% w/w and 3.06 ± 0.54% w/w, respectively. In terms of the degree of O-substitution of chitosan by PEG (DS_PEG) and the degree of substitution of PEG by galactose (DS_g) are 177.69% and 86.7%, respectively. Exclusively high DS_PEG indicates both C6–OH and C3–OH of chitosan are conjugated with PEG polymer chains. Further prominent attachment of galactose onto hydroxyl end group of PEG allows chitosan-O-PEG-galactose to possess sufficient quantity of targeting moieties for asialoglycoprotein receptor on hepatocytes.     

Hepatocyte adhesion on a poly[N-p-vinylbenzyl-4-O-beta-D-galactopyranosyl-D-glucoamide]-coated poly(L-lactic acid) surface

A surface of poly(l-lactic acid) (PLLA) was modified by coating with poly[N-p-vinylbenzyl-4-O-beta-d-galactopyranosyl-d-glucoamide] (PVLA), which was employed to improve the hepatocyte adhesion owing to its amphiphilic property and the presence of a hepatocyte recognition motif. We characterized the surface properties through water contact angle, electron spectroscopy for chemical analysis (ESCA), and scanning probe microscopy (SPM). The effect of PVLA coating on the efficiency of hepatocyte adhesion was evaluated by protein assay and optical microscopy. The surface morphology was under the influence of the concentration of PVLA coating solution and it played a critical role in hepatocyte adhesion. It was confirmed that galactose moieties in PVLA, which can bind to the asialoglycoprotein receptor (ASGPR) on hepatocytes, have a more dominant effect on hepatocyte adhesion than enhanced hydrophilicity. We suggest that the PVLA-PLLA system will be a useful method to improve hepatocyte cell seeding and adhesion onto scaffold matrices.     

Synthesis and characterization of star poly(epsilon-caprolactone)-b-poly(ethylene glycol) and poly(L-lactide)-b-poly(ethylene glycol) copolymers: evaluation as drug delivery carriers

Two types of 32 arm star polymers incorporating amphiphilic block copolymer arms have been synthesized and characterized. The first type, stPCL-PEG 32, is composed of a polyamidoamine (PAMAM) dendrimer as the core with radiating arms having poly(epsilon-caprolactone) (PCL) as an inner lipophilic block in the arm and poly(ethylene glycol) (PEG) as an outer hydrophilic block. The second type, stPLA-PEG 32, is similar but with poly(L-lactide) (PLA) as the inner lipophilic block. Characterization with SEC, (1)H NMR, FTIR, and DSC confirmed the structure of the polymers. Micelle formation by both star copolymers was studied by fluorescence spectroscopy. The stPCL-PEG 32 polymer exhibited unimolecular micelle behavior. It was capable of solubilizing hydrophobic molecules, such as pyrene, in aqueous solution, while not displaying a critical micelle concentration. In contrast, the association behavior of stPLA-PEG 32 in aqueous solution was characterized by an apparent critical micelle concentration of ca. 0.01 mg/mL. The hydrophobic anticancer drug etoposide can be encapsulated in the micelles formed from both polymers. Overall, the stPCL-PEG 32 polymer exhibited a higher etoposide loading capacity (up to 7.8 w/w % versus 4.3 w/w % for stPLA-PEG 32) as well as facile release kinetics and is more suitable as a potential drug delivery carrier.     

Amphiphilic triblock copolymers with PEGylated hydrocarbon structures as environmentally friendly marine antifouling and fouling-release coatings

The ideal marine antifouling (AF)/fouling-release (FR) coating should be non-toxic, while effectively either resisting the attachment of marine organisms (AF) or significantly reducing their strength of attachment (FR). Many recent studies have shown that amphiphilic polymeric materials provide a promising solution to producing such coatings due to their surface dual functionality. In this work, poly(ethylene glycol) (PEG) of different molecular weights (M_w?=?350, 550) was coupled to a saturated difunctional alkyl alcohol to generate amphiphilic surfactants (PEG-hydrocarbon-OH). The resulting macromolecules were then used as side chains to covalently modify a pre-synthesized PS₈?_K-b-P(E/B)₂₅?_K-b-PI₁₀?_K (SEBI or K3) triblock copolymer, and the final polymers were applied to glass substrata through an established multilayer surface coating technique to prepare fouling resistant coatings. The coated surfaces were characterized with AFM, XPS and NEXAFS, and evaluated in laboratory assays with two important fouling algae, Ulva linza (a green macroalga) and Navicula incerta, a biofilm-forming diatom. The results suggest that these polymer-coated surfaces undergo surface reconstruction upon changing the contact medium (polymer/air vs polymer/water), due to the preferential interfacial aggregation of the PEG segment on the surface in water. The amphiphilic polymer-coated surfaces showed promising results as both AF and FR coatings. The sample with longer PEG chain lengths (M_w?=?550?g?mol^?1) exhibited excellent properties against both algae, highlighting the importance of the chemical structures on ultimate biological performance. Besides reporting synthesis and characterization of this new type of amphiphilic surface material, this work also provides insight into the nature of PEG/hydrocarbon amphiphilic coatings, and this understanding may help in the design of future generations of fluorine-free, environmentally friendly AF/FR polymeric coatings.