Chitosan Polyethylene Glycol Research Articles

Treatment of fir wood with chitosan and polyethylene glycol

Chitosan is a natural biopolymer, derived from chitin, which is used for wood modification. Polyethylene glycol (PEG) was reacted with wood to provide possible fixation of the chitosan to wood. Wood blocks were treated with chitosan and PEG, as well as pre-treatment with the PEG at different temperatures and further reaction with the chitosan. The samples were soaked in water to study leaching of the chemicals, water absorption, swelling, as well as anti-swelling efficiency. Any prior reaction of the wood with PEG provided better reaction to the chitosan. Bulking was increased after the treatment of the wood with PEG. Swelling was reduced in the PEG-treated wood blocks as well as the pre-treated samples. Chitosan was not able to protect wood against water penetration: the treated samples showed more water absorption and swelling. However, pre-treatment of the samples decreased swelling in the wood, and the density was not noticeably affected by the treatments. Heating during the treatment caused more reduction in swelling for PEG–chitosan treated samples.

Enzyme-mediated fabrication of an oxidized chitosan hydrogel as a tissue sealant

Oxidized polysaccharide-based hydrogels have recently attracted much attention for tissue regeneration because of their biocompatibility and tissue-adhesive property. In this study, we introduce a new type of chitosan-based hydrogel as a tissue sealant, which was prepared by enzymatic mediation from periodate-oxidized chitosan–polyethylene glycol–tyramine. The oxidized chitosan backbone was expected to enhance the interconnection between the hydrogel layer and collagen in the tissues via the Schiff-base reaction. Proton nuclear magnetic resonance spectra indicated that tyramine-functionalized polyethylene glycol-nitrophenyl carbonate ester was conjugated to the oxidized chitosan. The degree of oxidation of the chitosan backbone was around 14% of the glucosamine units by proton nuclear magnetic resonance. The hydrogel was rapidly formed in situ (within a few seconds) in the presence of horseradish peroxidase and hydrogen peroxide. In vitro experiments with live/dead cell assays showed that the oxidized chitosan-based hydrogel was cytobiocompatible. The hydrogel exhibited high tissue adhesion strength on porcine skin models as well as good tissue-adhesive ability and wound healing properties on rabbit skin. These positive results could be promising for the application of oxidized chitosan-based hydrogels as a wound sealant.

A hybrid modeling approach for optimization of PMAA–chitosan–PEG nanoparticles for oral insulin delivery

This study aimed to develop pH sensitive polymethacrylic acid–chitosan–polyethylene glycol (PCP) nanoparticles for oral insulin delivery.

Therapeutic targeting of chitosan–PEG–folate-complexed oncolytic adenovirus for active and systemic cancer gene therapy

Adenovirus (Ad)-based cancer therapies have shown much promise. However, until now, Ad has only been delivered directly to primary tumors because the therapeutic efficacy of systemic delivery is limited by the immune response of the host, short blood circulation times, and non-specific liver uptake of Ad. In order to circumvent the issues regarding systemic delivery and to increase the safety and efficacy of Ad therapies, the surface of oncolytic Ad was coated with cationic polymer chitosan via ionic crosslinking (Ad/chitosan), after which polyethylene glycol (PEG) and/or folic acid (FA) was chemically conjugated onto the surface of Ad/chitosan, generating Ad/chitosan–FA, Ad/chitosan–PEG, and Ad/chitosan–PEG–FA nanocomplex. The FA-coordinated Ad nanocomplexes (Ad/chitosan–FA & Ad/chitosan–PEG–FA) elicited folate receptor (FR)-selective cancer cell killing efficacy. In vivo administration of Ad/chitosan–PEG or Ad/chitosan–PEG–FA into mice demonstrated that PEGylation greatly increased blood circulation time, resulting in 9.0-fold and 48.9-fold increases at 24h after injection compared with naked Ad, respectively. In addition, generation of Ad-specific neutralizing antibodies in mice treated with Ad/chitosan–PEG–FA was markedly decreased by 75.3% compared with naked Ad. The quantitative polymerase chain reaction assay results showed a 285.0-fold increase in tumor tissues and a 378-fold reduction of Ad/chitosan–PEG–FA in liver tissues compared with naked Ad. Bioluminescence imaging study further supported the enhanced tumor-to-liver ratio of Ad/chitosan–PEG–FA. Consequently, systemic delivery of Ad/chitosan–PEG–FA significantly inhibited the growth of FR-positive tumor, decreasing 52.8% compared to the naked Ad-treated group. Importantly, PEGylated oncolytic Ad nanocomplexes showed no elevation of both alanine transaminase and aspartate transaminase levels, demonstrating that systemically delivered Ad-related hepatic damage can be completely eliminated with PEG conjugation. In sum, these results demonstrate that conjugation of chitosan–PEG–FA to oncolytic Ad significantly improves antitumor efficacy and safety profiles, suggesting that Ad/chitosan–PEG–FA has potential as a therapeutic agent to target FR-positive cancer via systemic administration.

Targeted siRNA delivery by anti-HER2 antibody-modified nanoparticles of mPEG-chitosan diblock copolymer

This study aims to determine the specificity of anti-human epidermal growth factor receptor antibody (anti-HER2) modified monomethoxy polyethylene glycol-chitosan (mPEG-CS) nanoparticles (anti-HER2/mPEG-CS NPs) in delivering small interfering RNA (siRNA) to the human epidermal growth factor receptor 2 (HER2) positive cancer cells. Physicochemical properties of the siRNA-loaded anti-HER2/mPEG-CS NPs (anti-HER2/mPEG-CS-siRNA NPs), including size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by particle size and zeta potential analyzer, and ultraviolet–visible spectrophotometer. MTT assay was used to study the in vitro cytotoxicity of the NPs. Fluorescent microscope and flow cytometer analysis results showed that anti-HER2/mPEG-CS-siRNA NPs had much efficient delivery of siRNA than the siRNA alone, Lipofectamine-siRNA complexes and mPEG-CS-siRNA NPs. These results demonstrated that anti-HER2/mPEG-CS-siRNA NPs had great potential applications as a targeted strategy for siRNA delivery.

Preparation and optimization of PMAA–chitosan–PEG nanoparticles for oral drug delivery

The objective of this study was to develop pH sensitive polymethacrylic acid–chitosan–polyethylene glycol (PCP) nanoparticles. This was achieved by dispersion polymerization of methacrylic acid (MAA), polyethylene glycol (PEG) and different chitosan (CS) grades in the presence of cross linking agent ethylene dimethacrylate (EDMA) and polymer initiator potassium persulphate. Method development was carried out by varying formulation parameters such as type of CS, ratio of PEG to CS, quantity of solvent and polymer initiator. Metoprolol (MTP) tartrate was incorporated into the nanoparticles (NPs) as a model drug. Laser diffraction, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed that the NPs were spherical with smooth surfaces ranging in size from 190 to 450 nm. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) findings showed the presence of amorphous MTP in PCP NPs. The MTP loading of PCP and glycol chitosan (GC) NPs varied from 10 to 45% depending on the CS grade while both types of NPs showed excellent binding efficiency on mucin from porcine stomach. The in vitro dissolution study showed pH dependent release profiles suggesting that the PCP NPs system have great potential for oral controlled drug delivery as an alternative to conventional dosage forms.

Degradation of PEG and non-PEG alginate–chitosan microcapsules in different pH environments

Bioencapsulation allows the protection of biologically active substances or cells from the biological environment. As such, bioencapsulation is often used for the delivery of drugs, growth factors and therapeutically useful cells. Depending on the site of implantation, the biocapsules are subjected to different pH environments, which will affect the degradation properties, mechanical properties and swelling behaviour of the biocapsules. As such, the encapsulation material plays an important role in the long term stability and performance of the biocapsules in vivo. In this study, five types of encapsulation materials were investigated: (i) alginate (A), (ii) alginate–chitosan (AC), (iii) alginate–chitosan–alginate (ACA), (iv) alginate–chitosan–polyethylene glycol (PEG) (ACP) and (v) alginate–chitosan–polyethylene glycol (PEG)–alginate (ACPA). Degradation studies were carried out by immersing the microcapsules in solutions of different pH values to investigate the role of the material as well as the number of encapsulation layers in maintaining the stability of the microcapsules in the different pH environments. Compression testing indicated that even with the presence of PEG on the surface membrane, there was not much difference in mechanical strength between ACA and ACPA microcapsules. However, the use of PEG did affect the weight change of the ACPA microcapsules when immersed in water and three different pH solutions. For the swelling test, the ACPA microcapsules showed a lower water uptake than ACA microcapsules. For degradation, the presence of PEG led to a lower increase in weight change compared to non-PEG chitosan microcapsules. Hence, the study revealed that PEG influenced the integrity of the surface membrane and not the mechanical strength of the microcapsules. With the inclusion of PEG, the interpenetrating network on the surface membrane would be further reinforced. As such, the addition of PEG to the alginate–chitosan microcapsules led to protection against an acidic environment, whilst the number of coating layers only influences the swelling properties and not the degradation and Young’s modulus of the microcapsules.

Microporous Composites Prepared by Coagulation of a CS/PEG Solution in NaOH

Novel biodegradable three-dimensional composites with a porous structure have been prepared by coagulation of a chitosan (CS)/poly ethylene glycol (PEG) solution in NaOH. It is confirmed that PEG acts not only as a modifier to improve the mechanical properties, but also as a porogen for the CS matrix to induce porous structure. The porous structure and mechanical properties of the composites can be tailored with the amount of PEG and glutaraldehyde (GA). The addition of GA can improve the interaction strength and compatibility between the PEG phase and CS matrix. The resulting composites have smaller pore size, lower porosity, and better mechanical properties.

Cyclodextrin complexed insulin encapsulated hydrogel microparticles: An oral delivery system for insulin

An oral insulin delivery system based on methyl-β-cyclodextrin (MCD) complexed insulin encapsulated polymethacrylic acid (PMAA) hydrogel microparticles was evaluated in this investigation. Poly(methacrylic acid)-chitosan-polyethylene glycol (PCP) microparticles were prepared by ionic gelation method. The insulin–MCD (IC) complex prepared was characterized by fluorescence spectroscopic and isothermal titration micro-calorimeteric (ITC) methods. MCD complexed insulin was encapsulated onto PCP microparticles by diffusion filling method. Loading and release properties of the complexed insulin from microparticles were evaluated under in vitro conditions. The effect of MCD complexation on the permeability of insulin was studied using Caco 2 cell monolayers and excised intestinal tissue with an Ussing chamber set-up. In vivo experiments were carried on streptozotocin induced diabetic rats to evaluate the efficacy of MCD complexed insulin encapsulated PCP microparticles to deliver insulin by the oral route. IC complex formation was established by fluorescence and ITC investigations. Insulin loading and release properties from the hydrogel matrix was rather unaffected by the MCD complexation. However MCD complexation was effective in enhancing insulin transport across Caco 2 cell monolayers, when applied in combination with the PMAA hydrogel system. Both insulin and MCD complexed insulin encapsulated PCP microparticles were effective in reducing blood glucose level in diabetic animal models. Cyclodextrin complexed insulin encapsulated hydrogel microparticles appear to be an interesting candidate for oral delivery of insulin.

Kinetics of coacervation transition versus nanoparticle formation in chitosan–sodium tripolyphosphate solutions

Chitosan (deacetylation = 75–85%) and sodium tripolyphosphate (TPP) solutions were observed to undergo spontaneous coacervation transition or nanoparticle formation depending on the chitosan concentration and the volumetric mixing ratio [chitosan/TPP]. Three distinct conditions have been identified: (i) [chitosan] ≤ 0.5 mg/ml, 0.5 ≤ [chitosan/TPP] ≤ 2 and pH < 5.5, yields spontaneous coacervation, (ii) 0.5 ≤ [chitosan] ≤ 2.5 mg/ml, [chitosan/TPP] ≥ 2 and 3.5 < pH < 5.5, produces chitosan nanoparticles and (iii) 0.5 ≤ [chitosan] ≤3 mg/ml, 3 ≤ [chitosan/TPP] ≤ 6 and 5 <pH < 7.5, favors induced coacervation. Sizing done by TEM and dynamic light scattering studies revealed that chitosan nanoparticles had typical diameter in the range ≈150–350 nm depending on polymer concentration and chitosan/TPP mixing ratio, which reduced by ≈40% when polyethylene glycol (PEG) was added to these solutions. The long-time light scattering probing of the solutions revealed that residual interactions continuously produced soluble intermolecular complexes over extended period of time, a process that enabled the generation of coacervate droplets seamlessly. The coacervates (formed spontaneously or induced), and chitosan and chitosan–PEG nanoparticles, were used for encapsulating hydrophobic protein synthesis inhibitor model drug cycloheximide. The comparative in vitro release profiles in phosphate buffer and simulated intestinal fluid was monitored at 37 °C.

Synthesis, characterization and cytotoxicity of photo-crosslinked maleic chitosan–polyethylene glycol diacrylate hybrid hydrogels

Synthetic hydrogels are important biomaterials for many biomedical applications and hydrogels produced via photo-gelation have shown particular promise. In this paper, we describe a new family of biodegradable hybrid hydrogels fabricated in aqueous solution via long wavelength UV photo-crosslinking using maleic chitosan and polyethylene glycol diacrylate (PEGDA) as precursors. The maleic chitosan precursor was prepared by a simple one-step chemical modification of chitosan, with high yields, and characterized by Fourier transform infrared spectroscopy, (1)H NMR and (13)C NMR. Maleic chitosan and PEGDA precursors at a wide range of weight feed ratios were mixed in aqueous solution and directly photo-crosslinked for 10 min under a long wavelength UV light (365 nm) using 4-(2-hydroxyethoxy) phenyl-(2-hydroxy-2-propyl) ketone (Irgacure 2959) as photoinitiator. It was observed that as the weight feed ratio of maleic chitosan to PEGDA decreased the pore sizes of the hydrogel samples decreased, thereby increasing the densities of the hydrogel networks and producing a lower swelling ratio and a higher compressive modulus. The molecular weight of PEGDA had a similar effect. Preliminary cell cytotoxicity tests of both the maleic chitosan precursor and maleic chitosan/PEGDA hydrogels, based on the MTT assay and live-dead assay, respectively, showed that these new chitosan-based biodegradable biomaterials were relatively non-toxic to bovine aortic endothelial cells at low dosages.

Commentary [Research Highlights

Drug delivery to the central nervous system remains a vexing problem because of the presence of the blood-brain barrier (BBB), whose endothelial cell tight junctions limit the paracellular flux of hydrophilic molecules. One solution may be vector-mediated delivery to the brain. This employs chimeric peptide technology, wherein the drug is conjugated to a molecular carrier of protein nature (e.g. cationized albumin or a transferrin receptor antibody). Transferrin receptor antibodies selectively target BBB endothelium due to the high levels of receptor expressed by these cells, thereby triggering receptor-mediated transport across the BBB via transcytosis. Chitosan, a naturally occurring, abundant, and biocompatible polysaccharide has found widespread pharmaceutical application. In particular, the cationic nature of chitosan facilitates its interaction with negative charges on the brain endothelium, Building on their previous work on brain-deliverable chitosan-polyethylene glycol nanoparticles functionalized with monoclonal anti-transferrin antibody, Karatas and colleagues have now designed caspase-3 inhibitor-loaded chitosan nanospheres conjugated with an anti-mouse transferrin receptor monoclonal antibody that selectively recognizes the transferrin receptor type 1 on the cerebral vasculature. Caspase-3 has been implicated in neuronal cell death in cerebral ischemia, as well as in the pathophysiology of other neurological disorders. When given intravenously, the caspase-3-loaded nanospheres were rapidly transported across the BBB and dose-dependently decreased infarct volume, neurological deficit, and ischemiainduced caspase-3 activity in mice subjected to focal cerebral ischemia/reperfusion. Because significant opening of the BBB starts only 6 h after ischemia/reperfusion, the rapid transfer of nanospheres to the brain was not likely caused by an increased permeability of the BBB. Similarly, nanospheres inhibited physiological caspase-3 activity during development in the neonatal mouse cerebellum on postnatal day 17, after closure of the BBB. These observations convincingly demonstrate that transferrin monoclonal antibody-conjugated chitosan nanospheres are an efficient delivery system for bringing neuroprotective, small peptide drugs into the brain. This opens intriguing new avenues for the treatment of central nervous system disorders in which the administration of therapeutic agents is handicapped by insufficient diffusion across the BBB. Further studies are eagerly awaited to see if this technology will be applicable to polypeptide factors, for example, brain-derived neurotrophic factor and ciliary neurotrophic factor.

Preparation of chitosan–polyethylene glycol coated cotton membranes for wound dressings: preparation and characterization

AbstractCotton fabric was coated with chitosan (CS) and polyethylene glycol (PEG) followed by freeze‐drying. The influence of PEG on the physical characteristics and the surface morphology was investigated. The scanning electron microscopy of the coated fabric revealed a porous structure. The porosity of the material was 54–70% and the pore size was in the range of 75–120µm. The increase in the PEG content in the blend composition led to an enhanced destabilization of pores, leading to an increase in the pore size with elongated morphology. There seems to be phase separation between the two components which is an important factor for the observed behavior of the porous structure. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) showed that the CS and PEG have limited interaction. DSC suggested that addition of PEG to CS does not interfere with the crystallization behavior due to limited interaction with CS. The thermogravimetric analysis (TGA) showed that the membranes are thermally stable and PEG enhances the thermal stability of the CS coated membranes. The air and water permeability of the membranes tended to decrease with the increase in the PEG content. Copyright © 2008 John Wiley &amp; Sons, Ltd.

Biodegradation behavior and cytotoxicity of the composite membrane composed of beta-dicalcium pyrophosphate and glucose mediated (polyethylene glycol/chitosan).

The purpose of this study is to prepare and evaluate the biodegradation behavior and cytotoxicity of a composite membrane, G-beta-DCP, combining beta-dicalcium pyrophosphate (beta-DCP) ceramic particles and glucose mediated chitosan-polyethylene glycol (PEG) membrane. The cytotoxicity of the G-beta-DCP was examined by the in vitro method of NIH 3T3 fibroblast cell culture. Extracts were obtained by soaking the G-beta-DCP composite in lysozyme containing phosphate buffer solution for 2, 7, 14, 21 and 28 days, respectively. The substances released from the G-beta-DCP composite were analyzed by gas chromatography-mass spectrometry (GC-MAS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). The change in morphologies, chemical composition and crystal structure was examined by scanning electron microscopy (SEM) and X-ray diffraction pattern (XRD). The results of extracts cocultured with fibroblasts show that the growth of fibroblasts would increase for the extracts obtained from different beta-DCP feeding weight G-beta-DCP composites after soaking for 7 days. After further increasing the soaking time, the cell number still increases. It is found that the glucose amine and calcium are gradually released from the G-beta-DCP composites, which is considered to be nutritious for the growth of the fibroblast. The release rate of calcium ion and glucosamine concentration can be regulated by feeding the beta-DCP. The degradation behavior of G-beta-DCP composite is considered as an "onion degradation model" that the G-beta-DCP degrades from outer layer to inner layer. The developed material should have a great potential as a cell substrate in the field of tissue engineering.

Preparation and characterization of pH sensitive sugar mediated (polyethylene glycol/chitosan) membrane.

Novel biodegradable membrane based on chitosan matrix was prepared and characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and swelling test. Native sugar, which is commonly used in human life, was utilized to prepare the crosslinked hydrophilic chitosan-polyethylene glycol (PEG) polyblend. According to TGA and FTIR results, the chemical reaction occurred in imine bonds (C=N) between sugar and amino groups in chitosan. Chitosan blending with high swelling capacity of PEG increased the water affinity and reacted with sugar decreased the water affinity. The equilibrium water content (EWC) value of the sugar mediated membrane is in the sequence of sucrose>D-fructose>glucose and they all present much lower water uptake ability than polyblend. The chitosan was not degraded by lysozyme, but all of the sugar-mediated membranes were susceptible to lysozyme. Scanning electron microscope (SEM) morphology shows that the degradation rate not only was controlled by the chemical complexation between sugar and polyblends, but the surface morphology of membranes also has great influence. Sucrose-mediated membrane supports the attachment and growth of NIH 3T3 fibroblasts. The pH-sensitive and well degradable property of the sucrose-mediated membrane can be applied for biomedical application.