Grafted Carboxymethyl Chitosan Research Articles

Itaconic acid grafted carboxymethyl chitosan and its nanoparticles: Preparation, characterization and evaluation

This work aims to synthesize a novel itaconic acid (IA) grafted carboxymethyl chitosan (PICMCS), and further fabricate its nanoparticles for potential biomedical applications. First, PICMCS was prepared via free-radical polymerization of IA monomer, in the presence of ammonium persulfate as an initiator and nitrogen as a protector. Its chemical structure was confirmed by FTIR and 1H NMR. The IA substitution degree calculated by elemental analysis data was 1.85, implying that IA was successfully grafted to carboxymethyl chitosan (CMCS). XRD and TGA patterns illustrated its well-defined crystallinity and thermostability. Second, PICMCS nanoparticles were fabricated by electrostatic attraction between carboxyl and amino groups in the absence of any additional agent, which were of obvious core-shell structures with an average particle size of 144nm and a polydispersity index of 0.11. PICMCS nanoparticles exhibited excellent physical stability after storage at 25°C for 30days, without any aggregation. PICMCS nanoparticles with high negative surface charge also indicated the good stability, especially in neutral or alkaline media. Additionally, the cytotoxicity experiments showed that either PICMCS or its nanoparticles had better cytocompatibility toward L929 cells than CMCS. These findings above suggested that PICMCS was a kind of promising material for preparing nanoparticles used in biomedical field.

Inclusion-Interaction Assembly Strategy for Constructing pH/Redox Responsive Micelles for Controlled Release of 6-Mercaptopurine

An inclusion-interaction assembly strategy was used to construct novel pH/redox responsive core-shell micelles with hydrophobic drug as the core and hydrophilic polymer as the shell. At first, a dimer of hydrophobic drug 6-mercaptopurine and a hydrophilic β-CD grafted carboxymethyl chitosan were synthesized. Then, a novel amphiphilic inclusion complex was prepared with the dimer being partially embedded into the cavity of β-CD moiety. It self-assembled into pH/redox responsive core-shell micelles in distilled water. TEM confirmed that the micelles possessed a spherical core-shell configuration with a mean size of about 160 nm. DLS showed that the micelles were stable in aqueous solution. Their particle diameters altered with pH values as well as glutathione (GSH) concentrations and respectively attained a maximum value at pH 6.0 and 20 mM GSH. Release profiles of 6-mercaptopurine showed a low release rate (about 27 wt% after 48 h) in pH 7.4 medium with 10 μM GSH, and a marked increase (over 88 wt% after 48 h) in pH 5.0 medium with 20 mM GSH. In vitro cytotoxicity test showed that the micelles had a dose-dependent toxicity for HeLa cells, indicating a great potential for controlled release of 6-mercaptopurine in tumor cells.

PEGylated carboxymethyl chitosan/calcium phosphate hybrid anionic nanoparticles mediated hTERT siRNA delivery for anticancer therapy

Lack of safe and effective delivery vehicle is the main obstacle for siRNA mediated cancer therapy. In this study, we synthesized a pH-sensitive polymer of PEG grafted carboxymethyl chitosan (PEG-CMCS) and developed anionic-charged hybrid nanoparticles of PEG-CMCS and calcium phosphate (CaP) for siRNA delivery through a single-step self-assembly method in aqueous condition. The formed nanoparticles with charge of around −8.25 mv and average diameter of 102.1 nm exhibited efficient siRNA encapsulation and enhanced colloidal and serum stability. The test in vitro indicated that the nanoparticles entered into HepG2 cells by endocytosis, and achieved endosomal escape of siRNA effectively due to the pH-responsive disassembly of nanoparticles and dissolution of CaP in the endosome. Reporter gene silencing assay showed that luciferase siRNA delivered by the anionic nanoparticles could achieve gene silencing efficacy comparable to that of conventional Lipofectamine 2000. Additionally, dramatic hTERT knockdown mediated by the anionic nanoparticles transfection induced significant apoptosis of HepG2 cells in vitro. After intravenous injection in tumor-bearing BALB/c nude mice, the nanoparticles specifically accumulated into tumor regions by EPR effect, leading to efficient and specific gene silencing sequentially. Most importantly, the nanoparticles carrying hTERT siRNA inhibited tumor growth significantly via silencing hTERT expression and inducing cells apoptosis in HepG2 tumor xenograft. Moreover, comprehensive safety studies of the nanoparticles confirmed their superior safety both in vitro and in vivo. We concluded that the PEG-CMCS/CaP hybrid anionic nanoparticles possessed potential as a safe and effective siRNA delivery system for anticancer therapy.

Preparation, characterization and antioxidant activity of phenolic acids grafted carboxymethyl chitosan

In this study, three phenolic acids including gallic acid (GA), caffeic acid (CA) and ferulic acid (FA) were grafted onto N,O-carboxymethyl chitosan (NOCC) by a free radical mediated grafting method. The grafted copolymers obtained were all water-soluble samples. UV–vis absorption peaks of the grafted copolymers shifted toward longer wavelengths. FT-IR spectroscopy of the grafted copolymers exhibited additional phenolic characteristics of the aromatic ring CC stretching within 1450–1650cm−1. NMR spectroscopy of the grafted copolymers showed new peaks at 6.2–7.6ppm assigned to the phenyl protons of phenolic acids. These results all confirmed the successful grafting of three phenolic acids to NOCC. The conjugation probably occurred at amine of NOCC and carboxyl groups of phenolic acids. The grafted copolymers exhibited decreased crystallinity as compared to NOCC and chitosan. Moreover, antioxidant activity in vitro assays showed that the antioxidant property decreased in the order of GA-g-NOCC>CA-g-NOCC>FA-g-NOCC>NOCC>chitosan. Our results suggested the potential of phenolic acids grafted NOCC for the development of effective antioxidant agents.

PH-sensitive interpenetrating network hydrogels based on chitosan derivatives and alginate for oral drug delivery

Methoxy poly (ethylene glycol) grafted carboxymethyl chitosan (mPEG-g-CMC) and alginate were chosen as the constituents of hydrogel beads for the construction of an interpenetrating polymeric network matrix. A contrast study between the mPEG-g-CMC hydrogel and mPEG physically mixed with CMC hydrogel was carried out. Bovine serum albumin (BSA) as a model for a protein drug was encapsulated in the hydrogel network, and the drug release properties were studied. The hydrogels prepared by these two methods maintained good pH sensitivity; the loading capacity of the mPEG-g-CMC/alginate hydrogel was enhanced in comparison with that of the hydrogel prepared by physically mixing mPEG. The burst release of the protein was slightly decreased at pH 1.2, while the release at pH 7.4 was improved, suggesting that the mPEG-g-CMC/alginate pH-sensitive hydrogel will be promising for site-specific protein drug delivery in the intestine.

Doxorubicin-incorporated nanoparticles composed of poly(ethylene glycol)-grafted carboxymethyl chitosan and antitumor activity against glioma cells in vitro

In this study, methoxy poly(ethylene glycol)-grafted carboxymethyl chitosan (CMCPEG) was synthesized to make nanoparticles with doxorubicin (DOX) by ion complex formation. Since DOX has positive amine groups, it can interact with the carboxymethyl group of CMCPEG. The particle size of DOX-incorporated nanoparticles of CMCPEG was <300 nm and nanoparticles had spherical shapes at morphological observation, indicating that DOX/CMCPEG mixtures can form spherical nanoparticles. In a drug release study, higher drug content induced an extended release of drug. Drug release was significantly changed by the release media pH. DOX release was faster at an acidic pH than a neutral or basic pH. The antitumor activity of DOX-incorporated nanoparticles in vitro was tested with DOX-resistant C6 glioma cells. Nanoparticles showed increased cytotoxicity compared to DOX alone. These results suggest that DOX was unable to penetrate into cells and did not effectively inhibit cell proliferation. In contrast, nanoparticles can penetrate into cells and effectively inhibit cell proliferation. Observation of cells under red fluorescence confirmed these results, i.e., nanoparticle-treated C6 cells, unlike DOX-treated cells, had strong red fluorescence. Since DOX has strong red fluorescence, DOX-incorporated nanoparticles entered into the tumor cells more than DOX alone. As a result, we suggest that DOX-incorporated nanoparticles of CMCPEG are superior candidates for antitumor drug delivery.

Photo-induced synthesis, characterization and swelling behavior of poly(2-hydroxyethyl methacrylate) grafted carboxymethyl chitosan

In the present study, carboxymethyl chitosan was prepared and characterized. Photo-induced graft copolymerization of 2-hydroxyethyl methacrylate (HEMA) onto carboxymethyl chitosan (CMCs) was then carried out under nitrogen atmosphere in aqueous solution using 2,2-dimethoxy-2-phenyl acetophenone (PI) as photo-initiator. Grafting process was confirmed and the produced copolymers were characterized with aid of elemental analysis, FTIR, 2D-X ray diffraction, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The effects of HEMA and PI concentrations and the reaction time on the grafting yield were investigated by determining the grafting percentage and grafting efficiency. Under the applied experimental conditions, the optimum grafting conditions were obtained at: CMCs = 0.2 g, HEMA = 0.615 mol/L, PI = 0.0078 mol/L and reaction time = 90 min. The synthesized copolymers revealed a self-ability to form physically crosslinked hydrogels. The hydrogel nature of the copolymers was investigated by studying the solubility profiles and the cyclic swelling–deswelling behavior of copolymers with different grafting extents. These investigations of the photo-synthesized graft copolymers showed that they can be tailored and exploited as promising carriers for drug delivery purposes.

Synthesis, characterization and antimicrobial activity of poly (N-vinyl imidazole) grafted carboxymethyl chitosan

Poly ( N -vinyl imidazole) (PNVI) has been grafted onto carboxymethyl chitosan in aqueous solution using potassium persulphate (KPS) as initiator. The effect of the monomer and initiator concentration, the reaction temperature and time on the grafting yield have been investigated. The maximum grafting yield was achieved at [KPS] = 8 × 10 −2 mol/L, [M] = 1 mol/L at reaction temperature = 60 °C within reaction time = 2.5 h. The grafted products were characterized by FTIR, elemental analysis, SEM photographs, solubility tests, thermal analysis and antibacterial activity. Grafted products have improved the antimicrobial activity of carboxymethyl chitosan.