Versatile carboxymethyl chitin and chitosan nanomaterials: a review.

Biocompatibility, biodegradability, and low cost of chitin and chitosan have drawn immense attention in many fields including medicine, bioinspired material science, pharmaceuticals, and agriculture. Their handling and processing are difficult owing to its insolubility in neutral aqueous solution or organic solvents. One of the methods used to improve the solubility characteristics of chitin and chitosan is chemical modification. Introducing a carboxymethyl group is the most advantageous method of increasing the solubility of chitosan at neutral and alkaline pH. Carboxymethyl chitin (CMC) and carboxymethyl chitosan (CMCS) are water soluble derivatives formed by introducing CH₂COOH function into the polymer which endows it with better biological properties. The functional group makes CMC/CMCS nanoparticles (NPs) efficient vehicles for the delivery of DNA, proteins, and drugs. This review provides an overview of the characteristics of CMC/CMCS NPs as well as fulfills the task of describing and discussing its important roles primarily in cancer nanomedicine detailing the targeted drug delivery aspect. The application of these NPs in imaging, agriculture, and textiles has also been highlighted. The review also elaborates the advantages of using the CMC and CMCS NPs for drug and gene delivery.

[1]  Eugene Khor,et al.  Chitosan-alginate PEC membrane as a wound dressing: Assessment of incisional wound healing. , 2002, Journal of biomedical materials research.

[2]  E. Khor,et al.  Preparation and characterization of chitin beads as a wound dressing precursor. , 2001, Journal of biomedical materials research.

[3]  I. Azuma,et al.  Bioactive chitin derivatives. Activation of mouse-peritoneal macrophages by O-(carboxymethyl)chitins. , 1986, Carbohydrate research.

[4]  Leyu Wang,et al.  Preparation and upconversion luminescence cell imaging of O-carboxymethyl chitosan-functionalized NaYF4:Yb3+/Tm3+/Er3+ nanoparticles , 2013 .

[5]  R. Tharanathan,et al.  Chitin/chitosan: modifications and their unlimited application potential—an overview , 2007 .

[6]  Hsing-Wen Sung,et al.  In vivo biocompatibility and degradability of a novel injectable-chitosan-based implant. , 2002, Biomaterials.

[7]  Jian Shen,et al.  Covalent immobilization of chitosan/heparin complex with a photosensitive hetero-bifunctional crosslinking reagent on PLA surface. , 2002, Biomaterials.

[8]  Hua Zheng,et al.  Preparation, characterization, and in vitro drug release behavior of 6-mercaptopurine-carboxymethyl chitosan , 2011 .

[9]  T. Ukai,et al.  Multifunctional Biocompatible Fluorescent Carboxymethyl Cellulose Nanoparticles , 2012 .

[10]  Hyun-Jin Park,et al.  The effect of carboxymethyl-chitosan on proliferation and collagen secretion of normal and keloid skin fibroblasts. , 2002, Biomaterials.

[11]  E. Khor,et al.  Porous chitin matrices for tissue engineering: Fabrication and in vitro cytotoxic assessment , 2001 .

[12]  Philippe Marteau,et al.  Health benefits and health claims of probiotics: bridging science and marketing , 2011, British Journal of Nutrition.

[13]  S. Nair,et al.  Novel carboxymethyl chitin nanoparticles for cancer drug delivery applications , 2010 .

[14]  E. Khor,et al.  Novel fabrication of open-pore chitin matrixes. , 2000, Biomacromolecules.

[15]  W. Phillips,et al.  Delivery of gamma-imaging agents by liposomes. , 1999, Advanced drug delivery reviews.

[16]  Seong-Cheol Park,et al.  Encapsulation of paclitaxel into lauric acid-O-carboxymethyl chitosan-transferrin micelles for hydrophobic drug delivery and site-specific targeted delivery. , 2013, International journal of pharmaceutics.

[17]  K. Yao,et al.  Preparation of oxidized glucose-crosslinked N-alkylated chitosan membrane and in vitro studies of pH-sensitive drug delivery behaviour. , 2002, Biomaterials.

[18]  T. Mach,et al.  Clinical usefulness of probiotics in inflammatory bowel diseases. , 2006, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[19]  Y Ikada,et al.  In vitro and in vivo degradation of films of chitin and its deacetylated derivatives. , 1997, Biomaterials.

[20]  B. Han,et al.  Synthesis, characterization and biological safety of O-carboxymethyl chitosan used to treat Sarcoma 180 tumor , 2011 .

[21]  S. Nair,et al.  Efficacy of tetracycline encapsulated O-carboxymethyl chitosan nanoparticles against intracellular infections of Staphylococcus aureus. , 2012, International journal of biological macromolecules.

[22]  Qiqing Zhang,et al.  Preparation and characterization of self-aggregated nanoparticles of cholesterol-modified O-carboxymethyl chitosan conjugates , 2007 .

[23]  Hua Zheng,et al.  Preparation, characterization, and tissue distribution in mice of lactosaminated carboxymethyl chitosan nanoparticles , 2011 .

[24]  S. T. Lee,et al.  Fabrication and characterization of a sponge-like asymmetric chitosan membrane as a wound dressing. , 2001, Biomaterials.

[25]  E. Ito,et al.  The action of lysozyme on partially deacetylated chitin. , 1978, European journal of biochemistry.

[26]  H. Park,et al.  Chemical characteristics of O-carboxymethyl chitosans related to the preparation conditions , 2003 .

[27]  T. Tan,et al.  Preparation of chitosan/ethylcellulose complex microcapsule and its application in controlled release of vitamin D2. , 2002, Biomaterials.

[28]  P. Ramesh,et al.  Microstructured microspheres of hydroxyapatite bioceramic , 2002, Journal of materials science. Materials in medicine.

[29]  S. Hirano,et al.  The blood compatibility of chitosan and N-acylchitosans. , 1985, Journal of biomedical materials research.

[30]  Haixiong Ge,et al.  Synthesis and characterization of chitosan-poly(acrylic acid) nanoparticles. , 2002, Biomaterials.

[31]  T. Cheng,et al.  A method for the preparation of silver nanoparticles using commercially available carboxymethyl chitosan and sunlight , 2013 .

[32]  Jia-cong Shen,et al.  Surface engineering of poly(D,L-lactic acid) by entrapment of chitosan-based derivatives for the promotion of chondrogenesis. , 2002, Journal of biomedical materials research.

[33]  E. Khor,et al.  Wound dressing with sustained anti-microbial capability. , 2000, Journal of biomedical materials research.

[34]  M. Ito,et al.  Effect of hydroxyapatite content on physical properties and connective tissue reactions to a chitosan-hydroxyapatite composite membrane. , 1999, Journal of biomedical materials research.

[35]  Z. Teng,et al.  Carboxymethyl chitosan-soy protein complex nanoparticles for the encapsulation and controlled release of vitamin D₃. , 2013, Food chemistry.

[36]  H. Park,et al.  Preparation of alginate/chitosan/carboxymethyl chitosan complex microcapsules and application in Lactobacillus casei ATCC 393 , 2011 .

[37]  Fu-Rong Chen,et al.  Multifunctional core-shell polymeric nanoparticles for transdermal DNA delivery and epidermal Langerhans cells tracking. , 2010, Biomaterials.

[38]  E. Khor,et al.  Chitosan-alginate-CaCl(2) system for membrane coat application. , 2001, Journal of pharmaceutical sciences.

[39]  R. Muzzarelli.  Carboxymethylated chitins and chitosans , 1988 .

[40]  M. Ferrari.  Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[41]  F. Mi,et al.  Chitin/PLGA blend microspheres as a biodegradable drug-delivery system: phase-separation, degradation and release behavior. , 2002, Biomaterials.

[42]  Mark E. Davis,et al.  Nanoparticle therapeutics: an emerging treatment modality for cancer , 2008, Nature Reviews Drug Discovery.

[43]  Xiaoyuan Ma,et al.  The synthesis of chitosan-based silver nanoparticles and their antibacterial activity. , 2009, Carbohydrate research.

[44]  K. Gupta,et al.  Drug release behavior of beads and microgranules of chitosan. , 2000, Biomaterials.

[45]  Feng Zhao,et al.  Preparation and histological evaluation of biomimetic three-dimensional hydroxyapatite/chitosan-gelatin network composite scaffolds. , 2002, Biomaterials.

[46]  T. Nagai,et al.  Pharmacokinetic characteristics and antitumor activity of the N-succinyl-chitosan-mitomycin C conjugate and the carboxymethyl-chitin-mitomycin C conjugate. , 1993, Biological & pharmaceutical bulletin.

[47]  Xiaohong Wang,et al.  Bone repair in radii and tibias of rabbits with phosphorylated chitosan reinforced calcium phosphate cements. , 2002, Biomaterials.

[48]  P. Potiyaraj,et al.  Layer-by-layer deposition of antimicrobial silver nanoparticles on textile fibers , 2006 .

[49]  H. Onishi,et al.  Preparation of CM-chitin microspheres by complexation with iron(III) in w/o emulsion and their biodisposition characteristics in mice. , 2000, Biomaterials.

[50]  S. Hirano,et al.  Wet spun chitosan-collagen fibers, their chemical N-modifications, and blood compatibility. , 2000, Biomaterials.

[51]  Juan Luo,et al.  Surface modification of poly (D,L-lactic acid) with chitosan and its effects on the culture of osteoblasts in vitro. , 2002, Journal of biomedical materials research.

[52]  J. Jung,et al.  Release of triamcinolone acetonide from mucoadhesive polymer composed of chitosan and poly(acrylic acid) in vitro. , 2002, Biomaterials.

[53]  Hua Zheng,et al.  Preparation, characterization and in vitro release study of a glutathione-dependent polymeric prodrug Cis-3-(9H-purin-6-ylthio)-acrylic acid-graft-carboxymethyl chitosan. , 2012, International journal of pharmaceutics.

[54]  Y. Machida,et al.  Biodegradation and distribution of water-soluble chitosan in mice. , 1999, Biomaterials.

[55]  T. Fujinaga,et al.  Accelerating effects of chitosan for healing at early phase of experimental open wound in dogs. , 1999, Biomaterials.

[56]  Xavier Duval,et al.  Growth factor receptor expression in anal squamous lesions: modifications associated with oncogenic human papillomavirus and human immunodeficiency virus. , 2009, Human pathology.

[57]  M. Alonso,et al.  Chitosan and Chitosan/Ethylene Oxide-Propylene Oxide Block Copolymer Nanoparticles as Novel Carriers for Proteins and Vaccines , 1997, Pharmaceutical Research.

[58]  T. Jesionowski,et al.  Poriferan Chitin as the Scaffold for Nanosilica Deposition under Hydrothermal Synthesis Conditions , 2013 .

[59]  T. Nagai,et al.  Conjugate of mitomycin C with N-succinyl-chitosan: In vitro drug release properties, toxicity and antitumor activity , 1993 .

[60]  M. Elsabee,et al.  Chitosan nanoparticle to carry vitamin C through the gastrointestinal tract and induce the non-specific immunity system of rainbow trout (Oncorhynchus mykiss) , 2011 .

[61]  W. Park,et al.  Blood compatibility and biodegradability of partially N-acylated chitosan derivatives. , 1995, Biomaterials.

[62]  S. Ko,et al.  Water-soluble chitin as a wound healing accelerator. , 1999, Biomaterials.

[63]  Y. Okahata,et al.  In vitro gene delivery mediated by chitosan. effect of pH, serum, and molecular mass of chitosan on the transfection efficiency. , 2001, Biomaterials.

[64]  K. Chennazhi,et al.  Chitosan conjugated DNA nanoparticles in gene therapy , 2010 .

[65]  Xiaohong Wang,et al.  Structural characterization of phosphorylated chitosan and their applications as effective additives of calcium phosphate cements. , 2001, Biomaterials.

[66]  P. Caliceti,et al.  Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[67]  Z. Xiufang,et al.  Studies on nerve cell affinity of chitosan-derived materials. , 2000, Journal of biomedical materials research.

[68]  W. Oyen,et al.  Radiolabeled liposomes for scintigraphic imaging. , 2000, Progress in lipid research.

[69]  S. Tatehara,et al.  The in vitro antibiotic release from anti-washout apatite cement using chitosan , 2002, Journal of materials science. Materials in medicine.

[70]  S. Hirano,et al.  Release of glycosaminoglycans in physiological saline and water by wet-spun chitin--acid glycosaminoglycan fibers. , 2001, Journal of biomedical materials research.

[71]  Toshihiro Akaike,et al.  Preparation of alginate/galactosylated chitosan scaffold for hepatocyte attachment. , 2002, Biomaterials.

[72]  S. Nair,et al.  O-carboxymethyl chitosan nanoparticles for metformin delivery to pancreatic cancer cells. , 2012, Carbohydrate polymers.

[73]  M. Yamabhai,et al.  Chitin Research Revisited , 2010, Marine drugs.

[74]  A. Sowmya,et al.  Removal of Phosphate from Aqueous Solution Using Hydrotalcite/Chitosan Composite , 2013 .

[75]  N. Selvamurugan,et al.  Chitosan and its derivatives for gene delivery. , 2011, International journal of biological macromolecules.

[76]  Y. Nimura,et al.  Effect of chitosan film containing basic fibroblast growth factor on wound healing in genetically diabetic mice. , 2003, Journal of biomedical materials research. Part A.

[77]  Miqin Zhang,et al.  Three-dimensional macroporous calcium phosphate bioceramics with nested chitosan sponges for load-bearing bone implants. , 2002, Journal of biomedical materials research.

[78]  Y. M. Lee,et al.  Synthesis and properties of poly(ethylene glycol) macromer/β-chitosan hydrogels , 1997 .

[79]  Thomas Rades,et al.  Immunostimulatory colloidal delivery systems for cancer vaccines , 2006, Expert opinion on drug delivery.

[80]  S Senel,et al.  Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for non-invasive vaccine delivery. , 2008, International journal of pharmaceutics.

[81]  M. Qiao,et al.  Preparation of N-succinyl-chitosan and its physical-chemical properties as a novel excipient. , 2006, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[82]  K. Zhu,et al.  Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure. , 2002, International journal of pharmaceutics.

[83]  Lingyun Chen,et al.  Relationships between the molecular structure and moisture-absorption and moisture-retention abilities of carboxymethyl chitosan. II. Effect of degree of deacetylation and carboxymethylation. , 2003, Carbohydrate research.

[84]  C. T. Chen,et al.  Porous chitosan microsphere for controlling the antigen release of Newcastle disease vaccine: preparation of antigen-adsorbed microsphere and in vitro release. , 1999, Biomaterials.

[85]  Y. Koyama,et al.  Preparation and microstructure analysis of chitosan/hydroxyapatite nanocomposites. , 2001, Journal of biomedical materials research.

[86]  Haojie Zhao,et al.  Novel sustained-release implant of herb extract using chitosan. , 2002, Biomaterials.

[87]  Dong-hong Li,et al.  Synthesis, biodegradability and cytotoxicity of water-soluble isobutylchitosan , 2007 .

[88]  R. Hoffmann,et al.  Modification of collagen in vitro with respect to formation of Nepsilon-carboxymethyllysine. , 2009, International journal of biological macromolecules.

[89]  J. Weng,et al.  Manufacture and evaluation of bioactive and biodegradable materials and scaffolds for tissue engineering , 2001, Journal of materials science. Materials in medicine.

[90]  M. Thanou,et al.  Biodegradation, biodistribution and toxicity of chitosan. , 2010, Advanced drug delivery reviews.

[91]  Y. Okamoto,et al.  Chitin and chitosan stimulate canine polymorphonuclear cells to release leukotriene B4 and prostaglandin E2. , 1998, Journal of biomedical materials research.

[92]  H. Sung,et al.  Stimuli-responsive materials prepared from carboxymethyl chitosan and poly(γ-glutamic acid) for protein delivery. , 2012, Carbohydrate polymers.

[93]  M. Risbud,et al.  Effect of chitosan-polyvinyl pyrrolidone hydrogel on proliferation and cytokine expression of endothelial cells: implications in islet immunoisolation. , 2001, Journal of biomedical materials research.

[94]  Qiang Wang,et al.  ErbB receptors: from oncogenes to targeted cancer therapies. , 2007, The Journal of clinical investigation.

[95]  C. Su,et al.  Development of fungal mycelia as skin substitutes: effects on wound healing and fibroblast. , 1999, Biomaterials.

[96]  Qingling Feng,et al.  Skeletal repair in rabbits with calcium phosphate cements incorporated phosphorylated chitin. , 2002, Biomaterials.

[97]  Shin Jung,et al.  Doxorubicin-incorporated nanoparticles composed of poly(ethylene glycol)-grafted carboxymethyl chitosan and antitumor activity against glioma cells in vitro. , 2010, Colloids and surfaces. B, Biointerfaces.

[98]  T. Chung,et al.  Growth of human endothelial cells on photochemically grafted Gly-Arg-Gly-Asp (GRGD) chitosans. , 2002, Biomaterials.

[99]  S. Meenakshi,et al.  Removal of Acid Blue 158 from Aqueous Media by Adsorption Onto Cross-Linked Chitosan Beads , 2013 .

[100]  T Lammers,et al.  Tumour-targeted nanomedicines: principles and practice , 2008, British Journal of Cancer.

[101]  M. Sastry,et al.  Chitosan Reduced Gold Nanoparticles as Novel Carriers for Transmucosal Delivery of Insulin , 2007, Pharmaceutical Research.

[102]  P. Low,et al.  Folate-targeted therapeutic and imaging agents for cancer. , 2009, Current opinion in chemical biology.

[103]  Steven A. Rosenberg,et al.  Cancer: Principles & Practice of Oncology: Annual Advances in Oncology , 2012 .

[104]  P. Watts,et al.  Cellular responses to chitosan in vitro: The importance of deacetylation , 2000, Journal of materials science. Materials in medicine.

[105]  K. Chennazhi,et al.  Efficient water soluble O-carboxymethyl chitosan nanocarrier for the delivery of curcumin to cancer cells , 2011 .

[106]  Ick Chan Kwon,et al.  Targeted delivery of low molecular drugs using chitosan and its derivatives. , 2010, Advanced drug delivery reviews.

[107]  F. Mi,et al.  Control of wound infections using a bilayer chitosan wound dressing with sustainable antibiotic delivery. , 2002, Journal of biomedical materials research.

[108]  Mohammad Reza Saboktakin,et al.  Synthesis and in vitro evaluation of carboxymethyl starch-chitosan nanoparticles as drug delivery system to the colon. , 2011, International journal of biological macromolecules.

[109]  A. Jemal,et al.  Cancer statistics, 2011 , 2011, CA: a cancer journal for clinicians.

[110]  S. Nair,et al.  Novel carboxymethyl derivatives of chitin and chitosan materials and their biomedical applications , 2010 .

[111]  S. Nair,et al.  O-Carboxymethyl Chitosan Nanoparticles for Controlled Release of Non-Steroidal Anti-Inflammatory Drugs , 2014 .

[112]  M. Murakami,et al.  Chitosan accelerates the production of osteopontin from polymorphonuclear leukocytes. , 2001, Biomaterials.

[113]  M. Ito.  In vitro properties of a chitosan-bonded hydroxyapatite bone-filling paste. , 1991, Biomaterials.

[114]  M. Murakami,et al.  Evaluation effects of chitosan for the extracellular matrix production by fibroblasts and the growth factors production by macrophages. , 2001, Biomaterials.

[115]  K. Song,et al.  β-Chitin-based wound dressing containing silver sulfurdiazine , 2000 .

[116]  S. Nair,et al.  Cetuximab conjugated O-carboxymethyl chitosan nanoparticles for targeting EGFR overexpressing cancer cells. , 2013, Carbohydrate polymers.

[117]  M. Endres,et al.  Biocompatible hydrogel supports the growth of respiratory epithelial cells: possibilities in tracheal tissue engineering. , 2001, Journal of biomedical materials research.

[118]  A. Wan,et al.  Preparation of a chitin-apatite composite by in situ precipitation onto porous chitin scaffolds. , 1998, Journal of biomedical materials research.

[119]  X Yan,et al.  PEC films prepared from Chitosan-Alginate coacervates. , 2000, Chemical & pharmaceutical bulletin.

[120]  R. Rolfe.  The role of probiotic cultures in the control of gastrointestinal health. , 2000, The Journal of nutrition.

[121]  Yan-jun Yang,et al.  Comparison of magnetic carboxymethyl chitosan nanoparticles and cation exchange resin for the efficient purification of lysine-tagged small ubiquitin-like modifier protease. , 2012, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[122]  K. Chennazhi,et al.  5-flourouracil loaded N,O-carboxymethyl chitosan nanoparticles as an anticancer nanomedicine for breast cancer. , 2012, Journal of biomedical nanotechnology.

[123]  S. Nair,et al.  Synthesis, characterization, cytotoxicity and antibacterial studies of chitosan, O-carboxymethyl and N,O-carboxymethyl chitosan nanoparticles , 2009 .

[124]  D. Williams.  Chitin: fulfilling a biomaterials promise - E. Khor; Elsevier, Amsterdam, 2001, pp. 136+xi, ISBN 0 08 044018 5 , 2002 .

[125]  E. Khor,et al.  The influence of anionic chitin derivatives on calcium phosphate crystallization. , 1998, Biomaterials.

[126]  S. Tokura,et al.  Effects of chitin and its derivatives on the proliferation and cytokine production of fibroblasts in vitro. , 1997, Biomaterials.

[127]  Hsin-Ell Wang,et al.  Nanotargeted Radionuclides for Cancer Nuclear Imaging and Internal Radiotherapy , 2010, Journal of biomedicine & biotechnology.

[128]  Y. Okamoto,et al.  Effects of chitin and chitosan particles on BALB/c mice by oral and parenteral administration. , 1997, Biomaterials.

[129]  S. Nair,et al.  Folate conjugated carboxymethyl chitosan–manganese doped zinc sulphide nanoparticles for targeted drug delivery and imaging of cancer cells , 2010 .

[130]  D. Horton,et al.  1,6-anhydro-2,3-O-isopropylidene-β-D-lyxo-hexopyranos-4-ulose , 1966 .

[131]  Makoto Kikuchi,et al.  Photocrosslinkable chitosan as a dressing for wound occlusion and accelerator in healing process. , 2002, Biomaterials.

[132]  U. Shinde,et al.  Development of Dorzolamide Loaded 6-O-Carboxymethyl Chitosan Nanoparticles for Open Angle Glaucoma , 2013, Journal of drug delivery.

[133]  M. Cilli,et al.  Ligand-targeted liposomal therapies of neuroblastoma. , 2007, Current medicinal chemistry.

[134]  Y. Ikada,et al.  Polymer-hydroxyapatite composites for biodegradable bone fillers. , 1986, Biomaterials.

[135]  C. Su,et al.  Fungal mycelia as the source of chitin and polysaccharides and their applications as skin substitutes. , 1997, Biomaterials.

[136]  A. Wan,et al.  Promotion of calcification on carboxymethylchitin discs. , 1996, Biomaterials.

[137]  S. Hirano,et al.  Novel method for the preparation of N-acylchitosan fiber and N-acylchitosan-cellulose fiber. , 1998, Biomaterials.

[138]  Y. Machida,et al.  Bioadhesive Characteristics of Chitosan Microspheres to the Mucosa of Rat Small Intestine , 2001, Drug development and industrial pharmacy.

[139]  Yujie Su,et al.  Separation of lysozyme using superparamagnetic carboxymethyl chitosan nanoparticles. , 2011, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[140]  Shilei Hao,et al.  Preparation and evaluation of O-carboxymethyl chitosan/cyclodextrin nanoparticles as hydrophobic drug delivery carriers , 2011 .

[141]  C. Mamot,et al.  Liposome-based approaches to overcome anticancer drug resistance. , 2003, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[142]  S. Haam,et al.  A novel pH-sensitive membrane from chitosan--TEOS IPN; preparation and its drug permeation characteristics. , 2001, Biomaterials.

[143]  Yingyu Zhou,et al.  A facile method for electrospinning of Ag nanoparticles/poly (vinyl alcohol)/carboxymethyl-chitosan nanofibers , 2012 .

[144]  Dan L. Longo,et al.  Cancer Chemotherapy and Biotherapy: Principles and Practice , 2001 .

[145]  H. Yagasaki,et al.  Histopathological and immunohistochemical studies of membranes of deacetylated chitin derivatives implanted over rat calvaria. , 1999, Journal of biomedical materials research.

[146]  C. Su,et al.  Cytotoxicity and immunogenicity of SACCHACHITIN and its mechanism of action on skin wound healing. , 2001, Journal of biomedical materials research.

[147]  T. Mai,et al.  Chitosan and O-carboxymethyl chitosan modified Fe3O4 for hyperthermic treatment , 2012 .

[148]  Cui Tang,et al.  Glycyrrhizin-modified O-carboxymethyl chitosan nanoparticles as drug vehicles targeting hepatocellular carcinoma. , 2012, Biomaterials.

[149]  H. Junginger,et al.  Enhancement of paracellular drug transport with highly quaternized N-trimethyl chitosan chloride in neutral environments: in vitro evaluation in intestinal epithelial cells (Caco-2). , 1999, Journal of pharmaceutical sciences.

[150]  E. Khor.  Chitin: a biomaterial in waiting , 2002 .

[151]  Xiguang Chen,et al.  Chitosan/o-carboxymethyl chitosan nanoparticles for efficient and safe oral anticancer drug delivery: in vitro and in vivo evaluation. , 2013, International journal of pharmaceutics.

[152]  C. Cho,et al.  A novel mucoadhesive polymer prepared by template polymerization of acrylic acid in the presence of chitosan. , 2001, Biomaterials.

[153]  Han-Joo Lee,et al.  Antibacterial effect of nanosized silver colloidal solution on textile fabrics , 2003 .

[154]  Qiqing Zhang,et al.  O-Carboxymethyl-chitosan/organosilica hybrid nanoparticles as non-viral vectors for gene delivery , 2009 .

[155]  S. Salminen,et al.  Probiotics: a role in the treatment of intestinal infection and inflammation? , 2002, Gut.

[156]  S. Nair,et al.  Electrospinning of carboxymethyl chitin/poly(vinyl alcohol) nanofibrous scaffolds for tissue engineering applications , 2009 .

[157]  R. Ruprecht,et al.  N-carboxymethylchitosan-N,O-sulfate as an anti-HIV-1 agent. , 1991, Biochemical and biophysical research communications.

[158]  D. Polk,et al.  Probiotics as functional food in the treatment of diarrhea , 2006, Current opinion in clinical nutrition and metabolic care.

[159]  K. Gupta,et al.  pH dependent hydrolysis and drug release behavior of chitosan/poly(ethylene glycol) polymer network microspheres , 2001, Journal of materials science. Materials in medicine.

[160]  J. Chen,et al.  A preliminary in vitro study on the fabrication and tissue engineering applications of a novel chitosan bilayer material as a scaffold of human neofetal dermal fibroblasts. , 2001, Biomaterials.

[161]  Danjun Wu,et al.  Preparation of Folate Conjugated O-Carboxymethyl Chitosan Nanoparticles , 2010 .

[162]  Gongjun Yang,et al.  O-Carboxymethylchitosan-based novel gatifloxacin delivery system , 2007 .

[163]  M. Nagayama,et al.  Tissue responses to anti-washout apatite cement using chitosan when implanted in the rat tibia , 2001, Journal of materials science. Materials in medicine.

[164]  M. Bibby,et al.  Pharmacological approach towards the development of indolequinone bioreductive drugs based on the clinically inactive agent EO9 , 2002, British journal of pharmacology.

[165]  C. Ling,et al.  Effects of dry heat and saturated steam on the physical properties of chitosan. , 1999, Journal of biomedical materials research.

[166]  H. Mizuguchi,et al.  Receptor-independent augmentation of adenovirus-mediated gene transfer with chitosan in vitro. , 2002, Biomaterials.

[167]  A. Tiwari,et al.  Carboxymethyl chitosan and its applications , 2010 .

[168]  Miqin Zhang,et al.  Synthesis and characterization of macroporous chitosan/calcium phosphate composite scaffolds for tissue engineering. , 2001, Journal of biomedical materials research.

[169]  Atsuro Yokoyama,et al.  Development of calcium phosphate cement using chitosan and citric acid for bone substitute materials. , 2002, Biomaterials.

[170]  M. Ishihara,et al.  Photocrosslinkable chitosan as a biological adhesive. , 2000, Journal of biomedical materials research.

[171]  J. Heller,et al.  Lysozyme degradation of partially deacetylated chitin, its films and hydrogels. , 1982, Biomaterials.

[172]  David Hui,et al.  Modern Applications of Nanotechnology in Textiles , 2008 .

[173]  T. Tanabe,et al.  Preparation and characterization of keratin-chitosan composite film. , 2002, Biomaterials.

[174]  Fanglian Yao,et al.  Synthesis and characterization of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core-shell nanoparticles. , 2012, Materials science & engineering. C, Materials for biological applications.

[175]  Qiang Zhang,et al.  Self-assembled nanoparticles based on galactosylated O-carboxymethyl chitosan-graft-stearic acid conjugates for delivery of doxorubicin. , 2013, International journal of pharmaceutics.

[176]  Miqin Zhang,et al.  Calcium phosphate/chitosan composite scaffolds for controlled in vitro antibiotic drug release. , 2002, Journal of biomedical materials research.

[177]  E. Khor,et al.  Chitosan-alginate films prepared with chitosans of different molecular weights. , 2001, Journal of biomedical materials research.

[178]  J. Crowston,et al.  Definition of glaucoma: clinical and experimental concepts , 2012, Clinical & experimental ophthalmology.

[179]  R. Hoffmann,et al.  Mineralization of biomimetically carboxymethylated collagen fibrils in a model dual membrane diffusion system , 2009 .

[180]  M. Morimoto,et al.  Effects of chitin/chitosan and their oligomers/monomers on migrations of fibroblasts and vascular endothelium. , 2002, Biomaterials.

[181]  A. Wan,et al.  Hydroxyapatite modified chitin as potential hard tissue substitute material. , 1997, Journal of biomedical materials research.

[182]  Shaker A Mousa,et al.  Emerging nanopharmaceuticals. , 2008, Nanomedicine : nanotechnology, biology, and medicine.

[183]  T. Nagai,et al.  Synthesis and drug-release characteristics of the conjugates of mitomycin C with N-succinyl-chitosan and carboxymethyl-chitin. , 1992, Chemical & pharmaceutical bulletin.

[184]  H. Park,et al.  Self-assembled nanoparticles based on linoleic-acid modified carboxymethyl-chitosan as carrier of adriamycin (ADR) , 2007 .