Synthesis and characterization of graft copolymer of chitosan and polyethylene glycol

MPEG was modified with 1,1′-carbonyldiimidazole, then the activated MPEG reacted with primary amino groups of chitosan. Synthesize the graft copolymer of chitosan and polyethylene glycol in two steps. The structure of the copolymer was characterized by FT-IR and 1H-NMR. It agrees with the PEG content of classical stealth nanoparticles materials. The X-ray diffraction and DSC analysis proved that the crystallinity of the copolymer increased. It is a promising material for the stealth nanoparticles. It is a potential new carrier for the drug delivery systems of long-circulation and solid carcinoma.     

One-pot synthesis of chitosan-g-(PEO-PLLA-PEO) via "click" chemistry and "SET-NRC" reaction

For the development of biocompatible and degradable biomaterials, a kind of well-defined graft copolymer consisting of chitosan back-bone and amphiphilic PEO-PLLA-PEO branch chains was synthesized by Cu(0) catalyzed one-pot strategy combining "click" chemistry and single electron transfer-nitroxide radical coupling (SET-NRC) reaction. First, the precursors of 6-azide-N-phthaloyl-chitosan, TEMPO-PEO-alkyne and mPEO-PLLA-Br were designed and produced. Then, the one-pot coupling reactions between these precursors were performed in the presence of nanosized Cu and PMDETA. The efficiencies of the coupling reactions were greater than 90% determined by the FTIR and ESR spectra. The structure of graft copolymer with 43% of the grafting ratio was confirmed by the spectral analysis. This work provided a route to prepare chitosan graft copolymer.     

Preparation of low molecular weight N-maleated chitosan-graft-PAMAM copolymer for enhanced DNA complexation

Low molecular weight N-maleated chitosan-graft-PAMAM (polyamidoamine) copolymer was prepared through N-maleated chitosan (NMC) by Michael type addition reaction to enhance its solubility in water as well as its cationic character for enhancement of DNA complexation. FTIR, (1)H NMR, XRD and GPC were used to characterize the graft copolymers. The copolymer showed better DNA complexation ability at low N/P ratio than that of chitosan due to increased surface charge density by the incorporation of PAMAM molecule on to chitosan backbone. The copolymer can effectively protect the DNA toward anionic surfactant. In vitro release study showed efficient DNA release occurred at physiological pH (pH 7.4). In vitro cell cytotoxicity test indicated toward less cytotoxicity of NMC-graft-PAMAM copolymers compared to that of 25kDa PEI. Thus, the synthesized NMC-graft-PAMAM copolymers have great potential of finding application in drug and gene delivery.     

Synthesis and self-assembly of chitosan-based copolymer with a pair of hydrophobic/hydrophilic grafts of polycaprolactone and poly(ethylene glycol)

Chitosan-based copolymers with binary grafts of hydrophobic polycaprolactone and hydrophilic poly(ethylene glycol) (CS-g-PCL&PEG) were prepared by a homogeneous coupling reaction of phthaloyl-protected chitosan with functional PCL-COOH and PEG-COOH, following deprotection to regenerate free amino groups back to chitosan backbone. They were characterized by ¹H NMR, Fourier transform infrared and X-ray diffraction analysis. These CS-g-PCL&PEG copolymers could form nano-size self-aggregates in acidic aqueous solution without a specific processing technique, which were investigated using dynamic light scattering and transmission electron microscopy. The formed self-aggregates become smaller with weakened stability upon pH increasing. Moreover, the aggregates of copolymer with higher content of PEG and PCL grafts could remain stable for over 30 days in both acid and neutral condition. A possible mechanism was proposed for the formation of self-aggregates from CS-g-PCL&PEG and their structural changes as pH. It is warranted to find promising application of these self-aggregates based on chitosan as drug carriers.     

Synthesis and property of chitosan graft copolymer by RAFT polymerization with tosylic acid-chitosan complex

pH- and thermo-sensitive (1→4)-2-amino-2-deoxy-β-d-glucan (i.e. chitosan) graft copolymer was prepared by reversible addition fragmentation chain transfer polymerizations of N-isopropylacrylamide with 4-methylbenzenesulfonic acid (i.e. tosylic acid)-chitosan complex. The polymerization was controlled well, and the amino group of chitosan could be deprotected easily and mildly with 15% Tris solution. The model aldehyde vanillin was conjugated with amino group of chitosan-g-PNIPAM via Schiff base bond (Loading efficiency, LE=77.6 mg/g), and the drug release could be controlled with temperature and pH. This property may promote the chitosan graft copolymer to be used in the field of "smart" drug delivery.     

Synthesis and properties of a water soluble graft (chitosan-g-2-acrylamidoglycolic acid) copolymer

The present paper reports the graft copolymerization of 2-acrylamidoglycolic acid onto chitosan by using potassium bromate/silver nitrate as an efficient redox initiator in an inert atmosphere. The effect of reaction conditions on grafting parameters i.e. grafting ratio, efficiency, conversion, add on, homopolymer and rate of grafting has been studied. Experimental results show that maximum grafting has been obtained at 0.4 g dm(-3) concentration of chitosan, 8.0×10(-2) mol dm(-3) concentration of 2-acrylamidoglycolic acid and 1.0×10(-3) mol dm(-3) concentration of hydrogen ion. It has also been observed that grafting ratio, add on, conversion, efficiency and rate of grafting increase up to 3.2×10(-3) mol dm(-3) of silver nitrate and 1.7×10(-2) mol dm(-3) of potassium bromate. Time (120 min) and temperature (40°C) were kept constant during reaction. The physicochemical properties of graft copolymer synthesized have been performed in terms of water swelling, metal ion sorption, flocculation and resistance to biodegradability with respect to the chitosan as a parent polymer. The graft copolymer has been characterized by Fourier transform infrared (FTIR) spectroscopy and thermogravimetric analysis.     

Preparation, characterization, and in vitro drug release behavior of biodegradable chitosan-graft-poly(1, 4-dioxan-2-one) copolymer

A novel copolymer of chitosan-g-poly(p-dioxanone) (CGP) was synthesized in bulk by ring-opening polymerization of p-dioxanone (PDO) initiated by the hydroxyl group or amino group of chitosan using SnOct₂ as catalyst. The chemical structure was determined by ¹H NMR. It was found that the feed ratio of chitosan to PDO had a great effect on the degree of polymerization (DP) and the substitution (DS) of PDO. The thermal stability and crystallization behavior of graft copolymer CGP were closely related to the values of DP and DS. When the resulting copolymer was used as Ibuprofen carrier, the release rate of Ibuprofen decreased compared with that of pure chitosan carrier. The drug release behavior was also influenced by the structure of graft copolymers.     

A chitosan-based flocculant prepared with gamma-irradiation-induced grafting

A natural polymer, chitosan, was modified to prepare an efficient flocculant using grafting method initiated by gamma ray in acid-water solution. A vinyl monomer, acrylamide, was used as the grafted monomer. The graft copolymer obtained was characterized using Fourier transform infrared spectroscopy, X-ray diffraction and thermogravimetric analysis. Effects of acetic acid concentration, total irradiation dose, dose rate and monomer concentration on the grafting percentage were investigated. Flocculation experiment results demonstrated that the graft copolymer produced was significantly superior to chitosan and polyacrylamide (PAM).     

Improvement in ductility of chitosan through blending and copolymerization with PEG: FTIR investigation of molecular interactions

Chitosan is an important biomaterial used widely in medical applications. One of the key concerns about its use is the fragile nature of chitosan films. By comparing the component molecular interactions using FTIR, this study attempts to understand how the ductility of chitosan can be improved by blending and copolymerizing with poly(ethylene glycol) (PEG). An improvement in ductility was obtained for all compositions of blend as manifested by a decrease in modulus and an increase in strain at break. For comparable PEG composition (approximately 30%), the properties of the solution-cast blend were better than those of the grafted copolymer. Therefore, blending may be a more efficient way to improve ductility of chitosan. FTIR characterization of the materials revealed subtle decreases in molecular interactions upon annealing the partially miscible blend. These may not be apparent in DSC or X-ray diffraction, yet they play a key role in the mechanical behavior. It appears that in the case of the graft copolymer the improvement in the properties comes from suppression of the crystallinity of each component and not from component interactions. On the other hand, in the blend, the improvement appears to come predominantly from the "well-dispersed", "kinetically trapped" phase morphology and from the intermolecular interactions. Therefore, annealing the blend leads to decreased intermolecular interactions, phase coarsening, and deterioration in properties.     

Preparation and spectroscopic characterization of methoxy poly(ethylene glycol)-grafted water-soluble chitosan

The object of this study was to test the solubility of a methoxy poly(ethylene glycol) (MPEG)-grafted chitosan copolymer in organic solvents and aqueous solution. Water-soluble chitosan with low molecular weight (LMWSC) was used in a PEG-graft copolymerization. The MPEG was conjugated to chitosan using 4-dicyclohexylcarbodimide (DCC), and N-hydroxysuccimide (NHS). Introduction of PEG was confirmed by (1)H and (13)C NMR spectroscopy and FT-IR spectroscopy. The degree of substitution (DS) of MPEG into chitosan was calculated from (1)H NMR data and also by estimating the molecular weight (MW) using gel permeation chromatography (GPC). The DS values obtained from (1)H NMR spectroscopy and GPC were similar, indicating that MPEG-grafted LMWSC was synthesized and properly characterized. Furthermore, the introduction of PEG into chitosan increases the solubility in aqueous solutions over a range of pH values (4.0-11.0) and organic solvents such as DMF, DMSO, ethanol, and acetone.     

Preparation of chitosan-g-polycaprolactone copolymers through ring-opening polymerization of epsilon-caprolactone onto phthaloyl-protected chitosan

The new biodegradable chitosan graft copolymer, chitosan-g-polycaprolactone, was synthesized by the ring-opening graft copolymerization of epsilon-caprolactone onto phthaloyl-protected chitosan (PHCS) at the hydroxyl group in the presence of tin(II) 2-ethylhexanoate catalyst via a protection-graft-deprotection procedure. Toluene acted as a swelling agent in this heterogeneous system. The grafting reactions were conducted with various PHCS/monomer/toluene feed ratios to obtain chitosan-g-polycaprolactone copolymers with various polycaprolactone contents. The chemical structure of the chitosan-g-polycaprolactone was characterized by Fourier transform infrared and one- and two-dimensional NMR spectroscopy. After deprotection, the phthaloyl group was removed and the amino group was regenerated. Thus the obtained chitosan-g-polycaprolactone was an amphoteric hybrid with a large amount of free amino groups and hydrophobic polycaprolactone side chains. Some properties of the final product were also investigated, such as crystallinity, thermal property, and solubility.     

Poly(L-lysine)-graft-chitosan copolymers: synthesis, characterization, and gene transfection effect

Polypeptide/polysaccharide graft copolymers poly(L-lysine)-graft-chitosan (PLL-g-Chi) were prepared by ring-opening polymerization (ROP) of epsilon-benzoxycarbonyl L-lysine N-carboxyanhydrides (Z-L-lysine NCA) in the presence of 6-O-triphenylmethyl chitosan. The PLL-g-Chi copolymers were thoroughly characterized by 1H NMR, 13C NMR, Fourier transform infrared (FT-IR), and gel permeation chromatography (GPC). The number-average degree of polymerization of PLL grafted onto the chitosan backbone could be adjusted by controlling the feed ratio of NCA to 6-O-triphenylmethyl chitosan. The particle size of the complexes formed from the copolymer and calf thymus DNA was measured by dynamic light scattering (DLS). It was found in the range of 120 approximately 340 nm. The gel retardation electrophoresis showed that the PLL-g-Chi copolymers possessed better plasmid DNA-binding ability than chitosan. The gene transfection effect in HEK 293T cells of the copolymers was evaluated, and the results showed that the gene transfection ability of the copolymer was better than that of chitosan and was dependent on the PLL grafting ratio. The PLL-g-Chi copolymers could be used as effective gene delivery vectors.     

Preparation and characterization of poly(acrylic acid)-hydroxyethyl cellulose graft copolymer

Poly(acrylic acid) hydroxyethyl cellulose [poly(AA)-HEC] graft copolymer was prepared by polymerizing acrylic acid (AA) with hydroxyethyl cellulose (HEC) using potassium bromate/thiourea dioxide (KBrO(3)/TUD) as redox initiation system. The polymerization reaction was carried out under a variety of conditions including concentrations of AA, KBrO(3) and TUD, material to liquor ratio and polymerization temperature. The polymerization reaction was monitored by withdrawing samples from the reaction medium and measuring the total conversion. The rheological properties of the poly(AA)-HEC graft copolymer were investigated. The total conversion and rheological properties of the graft copolymer depended on the ratio of KBrO(3) to TUD and on acrylic acid concentration as well as temperature and material to liquor ratio. Optimum conditions of the graft copolymer preparation were 30mmol KBrO(3) and 30mmol TUD/100g HEC, 100% AA (based on weight of HEC), duration 2h at temperature 50°C using a material to liquor ratio of 1:10.     

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.     

Synthesis of well-defined graft copolymers by combination of enzymatic polycondensation and "click" chemistry

Aliphatic polyesters having pendant azide groups were prepared by enzymatic polycondensation in the presence of lipase from Candida antarctica type B (CAL-B). The grafting reaction to the N(3)-functional polyester was carried out quantitatively at room temperature using copper-catalyzed azide-alkyne cycloaddition (CuAAC, "click" reaction) with monoalkyne-functional poly(ethylene oxide) (alkyne-PEO, M(n) = 750 g/mol). Furthermore, both enzymatic polycondensation and "click" reaction were carried out successfully in sequential one-pot reaction. The graft copolymer was surface-active and self-assembled in water. The graft copolymer had a critical aggregation concentration (cac) of 3 × 10(-2) μM in water determined by surface tension measurements. Above cac, the graft copolymer formed single chains and aggregates having a hydrodynamic radius of ～75 nm. Furthermore, the surface activity of the polymers at the air-water interface was studied by Langmuir trough measurements. The Langmuir isotherm of the graft polymer showed a pseudoplateau resulting from desorption of PEO chains into the subphase upon compression.     

Synthesis of anionic poly(ethylene glycol) derivative for chitosan surface modification in blood-contacting applications

To improve blood compatibility, chitosan surface was modified by the complexa-tion-interpenetration method using an anionic derivative of poly(ethylene glycol) (PEG). Methoxypoly(ethylene glycol) sulfonate (MPEG sulfonate)-modified chitosan was prepared by allowing the base polymer to swell in an acidic medium, followed by polyelectrolyte complexation and interpenetration of MPEG sulfonate with the chitosan matrix. Addition of a strong base collapsed the base polymer to permanently immobilize the modifying agent on the surface. Electron spectroscopy for chemical analysis (ESCA) confirmed the presence of MPEG sulfonate on chitosan and the high resolution Cls peak showed an increase in -C—O- which is indicative of the ethylene oxide residues. The number of adherent platelets and the extent of platelet activation was significantly reduced on MPEG sulfonate-modified chitosan. Compared to an average of more than 66 fully activated platelets on unmodified chitosan surface, only 3.0 contact-adherent platelets were present on MPEG sulfonate-modified chitosan. Plasma recalcification time, a measure of the intrinsic coagulation reaction, was about 11.5 min in contact with modified chitosan. The results of this study show that chitosan surface can be modified by the complexation-interpenetration method with anionic PEG derivative. Surface-immobilized MPEG sulfonate was effective in preventing plasma protein adsorption and platelet adhesion and activation by the steric repulsion mechanism.     

The use of graft copolymers to inhibit the adhesion of bacteria to solid surfaces

Twelve graft copolymers have been evaluated for their ability to prevent the adhesion of bacteria to substrata. The copolymers had polyethylene glycol (PEG) side-chains (‘teeth’) and a backbone that was either uncharged, acidic, basic or amphoteric. The copolymers were adsorbed onto glass, stainless steel and hydroxyapatite substrata, and 2-hpetri-dish adhesion experiments performed with bacteria isolated from marine (Pseudomonas sp. NCMB 2021), paper mill (S. marcescens NCIB 12211) and oral (S. mutans NCTC 10449) environments. The copolymers containing the most charged groups in the backbone had the most significant effect on bacterial adhesion levels, with anti-adhesive effects up to 99% achieved. An amphoteric copolymer (Compound 12) on glass, and acidic copolymer (Compound 11) on stainless steel and hydroxyapatite gave the most impressive anti-adhesive effects. These copolymers had non-specific bacterial anti-adhesive properties.It is proposed that the graft copolymers adsorbed onto hydrophilic surfaces via their charged backbone in such a way that the PEG side-chains were pointing out into the aqueous phase, and it was this orientation that was responsible for the observed anti-adhesive effect.     

Preparation, characterization, and properties of chitosan-g-poly(vinyl alcohol) copolymer

The graft copolymer chitosan-g-poly(vinyl alcohol), with nontoxicity, biodegradability, and biocompatibility, was prepared by a novel method. The copolymer with porous net structure was observed by scanning electron microscopy (SEM). It is a potential method to combine chitosan with the synthetic polymers. The grafting reactions were conducted with various poly(vinyl alcohol) (PVA)/6-O-succinate-N-phthaloyl-chitosan (PHCSSA) feed ratios to obtain chitosan-g-poly(vinyl alcohol) copolymers with various PVA contents. The chemical structure of the chitosan-g-poly(vinyl alcohol) was characterized by Fourier transform infrared and nuclear magnetic resonance (NMR) spectroscopy. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and SEM were also detected to characterize the copolymer.     

Synthesis and characterization of a brush-like copolymer of polylactide grafted onto chitosan

A brush-like poly(DL)-lactide grafted onto chitosan as the backbone was investigated. The graft copolymerization was carried out with triethylaluminum as catalyst in toluene at 70 degrees C. It was found that a greater lactide content in the feeding ratio results in a higher grafting percentage. FTIR spectrometry, (1)H NMR, DSC scanning, and wide-angle X-ray scattering, respectively, are used to characterize these branch copolymers. A copolymer has a definite melting point when the molar feeding ratio of lactide to chitosan is more than 10:1, and the deltaH of the copolymers increases with the feed ratio of lactide to chitosan in feeding.