Review Topical Sections

Degradation properties and metabolic activity of alginate and chitosan polyelectrolytes for drug delivery and tissue engineering applications

  • Received: 12 October 2015 Accepted: 12 November 2015 Published: 23 November 2015
  • Polysaccharides are long monosaccharide units which are emerging as promising materials for tissue engineering and drug delivery applications due to their biocompatibility, mostly good availability and tailorable properties, by to the wide possibility to modify chemical composition, structure—i.e., linear chain or branching—and polymer source (animals, plants, microorganisms). For their peculiar behaviour as polyelectrolites, polysaccharides have been applied in various forms, such as injectable hydrogels or porous and fibrous scaffolds—alone or in combination with other natural or synthetic polymers—to design bioinspired platforms for the regeneration of different tissues (i.e., blood vessels, myocardium, heart valves, bone, articular and tracheal cartilage, intervertebral discs, menisci, skin, liver, skeletal muscle, neural tissue, urinary bladder) as well as for encapsulation and controlled delivery of drugs for pharmaceutical devices. In this paper, we focus on the pH sensitive response and degradation behaviour of negative (i.e., alginate) and positive (i.e., chitosan) charged polysaccharides in order to discuss the differences in terms of metabolic activity of polyelectrolytes with different ionic strength for their use in drug delivery and tissue engineering area.

    Citation: Vincenzo Guarino, Tania Caputo, Rosaria Altobelli, Luigi Ambrosio. Degradation properties and metabolic activity of alginate and chitosan polyelectrolytes for drug delivery and tissue engineering applications[J]. AIMS Materials Science, 2015, 2(4): 497-502. doi: 10.3934/matersci.2015.4.497

    Related Papers:

  • Polysaccharides are long monosaccharide units which are emerging as promising materials for tissue engineering and drug delivery applications due to their biocompatibility, mostly good availability and tailorable properties, by to the wide possibility to modify chemical composition, structure—i.e., linear chain or branching—and polymer source (animals, plants, microorganisms). For their peculiar behaviour as polyelectrolites, polysaccharides have been applied in various forms, such as injectable hydrogels or porous and fibrous scaffolds—alone or in combination with other natural or synthetic polymers—to design bioinspired platforms for the regeneration of different tissues (i.e., blood vessels, myocardium, heart valves, bone, articular and tracheal cartilage, intervertebral discs, menisci, skin, liver, skeletal muscle, neural tissue, urinary bladder) as well as for encapsulation and controlled delivery of drugs for pharmaceutical devices. In this paper, we focus on the pH sensitive response and degradation behaviour of negative (i.e., alginate) and positive (i.e., chitosan) charged polysaccharides in order to discuss the differences in terms of metabolic activity of polyelectrolytes with different ionic strength for their use in drug delivery and tissue engineering area.

    [1] Robyt J (2001) Polysaccharides: energy storage. John Wiley & Sons.
    [2] Wang HM, Loganathan D, Linhardt RJ (1991) Determination of the pKa of glucuronic acid and the carboxy groups of heparin by 13C-nuclear-magnetic-resonance spectroscopy. Biochem J 278: 689-95. doi: 10.1042/bj2780689
    [3] Kyte J (1995) Structure in protein chemistry. New Yorg: Garland Publishing Inc.
    [4] Crouzier T, Boudou T, Picart C (2010) Polysaccharide-based polyelectrolyte multilayers. Curr Opin Colloid In 15: 417-426. doi: 10.1016/j.cocis.2010.05.007
    [5] Shukla RK (2011) Carbohydrate Molecules: An Expanding Horizon in Drug Delivery and Biomedicine. Crit Rev Ther Drug Carrier Syst 28: 255-292. doi: 10.1615/CritRevTherDrugCarrierSyst.v28.i3.20
    [6] Dumitriu S (2004) Polysaccharides: Structural Diversity and Functional Versatility. Second Edition Marcel Dekker: New York.
    [7] Andresen IL, Skipnes O, Smidsrod O, et al. (1977) Some biological functions of matrix components in benthic algae in relation to their chemistry and the composition of seawater. ACS SymSer 48: 361-381.
    [8] Sadoff HL (1975) Encystment and germination in Azotobactervinelandii. Bacteriol Rev 39: 516-539.
    [9] Haug A, Larsen B, Smidsrød O (1966) A Study of the Constitution of Alginic Acid by Partial Acid Hydrolysis. Acta Chem Scand 20: 183-190. doi: 10.3891/acta.chem.scand.20-0183
    [10] Simionescu CI, Popa VI, Rusan V, et al. (1976) The influence of structural units distribution on macromolecular conformation of alginic acid. Cell Chem Technol 10: 587-594.
    [11] Min KH, Sasaki SF, Kashiwabara Y, et al. (1977) Fine structure of SMG alginate fragment in the light of its degradation by alginate lyases of Pseudomonas sp. J Biochem 81: 555-562.
    [12] Harding SE, Varum KM, Stokke BT, et al. (1991) Molecular weight determination of polysaccharides. Adv Carbohydr Anal 1:63-144.
    [13] Martinsen A, Skjåk-Bræk G, Smidsrød O (1991) Comparison of different methods for determination of molecular weight and molecular weight distribution of alginates. Carbohydr Polym 15: 171-193. doi: 10.1016/0144-8617(91)90031-7
    [14] Smidsrød O, Haug A (1968) Dependence upon uronic acid composition of some ion-exchange properties of alginates. Acta Chem Scand 22:1989-1997. doi: 10.3891/acta.chem.scand.22-1989
    [15] Sikorski P, Mo F, Skjåk-Bræk G, et al. (2007) Evidence for Egg-Box-Compatible Interactions in Calcium−Alginate Gels from Fiber X-ray Diffraction. Biomacromolecules 8: 2098-2103. doi: 10.1021/bm0701503
    [16] Haug A, Smidsrod O (1970) Selectivity of some anionic polymers for divalent metal ions. Acta Chem Scand 24: 843-854. doi: 10.3891/acta.chem.scand.24-0843
    [17] Haug A, Myklestad S, Larsen B, et al. (1967) Correlation between chemical structure and physical properties of alginates. Acta Chem Scand 21: 768-778. doi: 10.3891/acta.chem.scand.21-0768
    [18] Grasselli M, Diaz LE, Cascone O (1993) Beaded matrices from cross-linked alginate for affinity and ion exchange chromatography of proteins. Biotechnol Tech 7: 707-712. doi: 10.1007/BF00152617
    [19] Pawar SN, Edgar KJ (2012) Alginate derivatization: a review of chemistry, properties and application. Biomaterials 33: 3279-3305. doi: 10.1016/j.biomaterials.2012.01.007
    [20] Hari PR, Chandy T, Sharma CP (1996) Chitosan/calcium alginate beads for oral delivery of insulin. J Appl Polym Sci 59: 1795-1801. doi: 10.1002/(SICI)1097-4628(19960314)59:11<1795::AID-APP16>3.0.CO;2-T
    [21] Huguet ML, Groboillot A, Neufeld RJ, et al. (1994) Hemoglobin encapsulation in chitosan/calcium alginate beads. J Appl Polym Sci 51: 1427-1432. doi: 10.1002/app.1994.070510810
    [22] MiFL, Sung HW, Shyu SS (2002) Drug release from chitosan-alginate complex beads reinforced by a naturally occurring crosslinking agent. Carbohydr Polym 48: 61-72. doi: 10.1016/S0144-8617(01)00212-0
    [23] Chan AW, Whitney RA, Neufeld R (2009) Semisynthesis of a controlled stimuli-responsive alginate hydrogel. Biomacromolecules 10: 609-616. doi: 10.1021/bm801316z
    [24] Bhattarai N, Zhang M (2007) Controlled synthesis and structural stability of alginate-based nanofibers. Nanotechnology 18: 455601-455611. doi: 10.1088/0957-4484/18/45/455601
    [25] Bouhadir KH, Hausman DS, Mooney DJ (1999) Synthesis of cross-linked poly(aldehyde guluronate) hydrogels. Polymer 40: 3575-3584. doi: 10.1016/S0032-3861(98)00550-3
    [26] Xu JB, Bartley JP, Johnson RA (2003) Preparation and characterization of alginate hydrogel membranes crosslinked using a water-soluble carbodiimide. J Appl Polym Sci 90: 747-753. doi: 10.1002/app.12713
    [27] Boontheekul T, Kong HJ, Mooney DJ (2005) Controlling alginate gel degradation utilizing partial oxidation and bimodal molecular weight distribution. Biomaterials 26: 2455-2465. doi: 10.1016/j.biomaterials.2004.06.044
    [28] Gomez CG, Rinaudo M, Villar MA (2007) Oxidation of sodium alginate and characterization of the oxidized derivatives. Carbohydr Polym 67: 296-304. doi: 10.1016/j.carbpol.2006.05.025
    [29] Kang HA, Jeon GJ, Lee MY, et al. (2002) Effectiveness test of alginate-derived polymeric surfactants. J Chem Technol Biot 77: 205-210. doi: 10.1002/jctb.550
    [30] Kang HA, Shin MS, Yang JW (2002) Preparation and characterization of hydrophobically modified alginate. Polym Bull 47: 429-435. doi: 10.1007/s002890200005
    [31] Laurienzo P, Malinconico M, Motta A, et al. (2005) Synthesis and characterization of a novel alginate-poly(ethylene glycol) graft copolymer. Carbohydr Polym 62: 274-282. doi: 10.1016/j.carbpol.2005.08.005
    [32] Skjåk-Bræk G, Zanetti F, Paoletti S (1989) Effect of acetylation on some solution and gelling properties of alginates. Carbohydr Res 185: 131-138. doi: 10.1016/0008-6215(89)84028-5
    [33] Coleman RJ, Lawrie G, Lambert LK, et al. (2011) Phosphorylation of alginate: synthesis, characterization, and evaluation of in vitro mineralization capacity. Biomacromolecules 12: 889-897. doi: 10.1021/bm1011773
    [34] Freeman I, Kedem A, Cohen S (2008) The effect of sulfation of alginate hydrogels on the specific binding and controlled release of heparin-binding proteins. Biomaterials 29: 3260-3268. doi: 10.1016/j.biomaterials.2008.04.025
    [35] Sand A, Yadav M, Mishra DK, et al. (2010) Modification of alginate by grafting of N-vinyl-2-pyrrolidone and studies of physicochemical properties in terms of swelling capacity, metal-ion uptake and flocculation. Carbohydr Polym 80: 1147-1154. doi: 10.1016/j.carbpol.2010.01.036
    [36] Sinquin A, Hubert P, Dellacherie E (1993) Amphiphilic derivatives of alginate: evidence for intra-and intermolecular hydrophobic associations in aqueous solution. Langmuir 9: 3334-3337. doi: 10.1021/la00036a002
    [37] Yang JS, Zhou QQ, He W (2013) Amphipathicity and self-assembly behavior of amphiphilic alginate esters. Carbohydr Polym 92: 223-227. doi: 10.1016/j.carbpol.2012.08.100
    [38] Mahou R, Meier RPH, Bühler LH, et al. (2014) Alginate-Poly(ethylene glycol) Hybrid Microspheres for Primary Cell Microencapsulation. Materials 7: 275-286. doi: 10.3390/ma7010275
    [39] Bernkop-Schnurch A, Kast CE, Richter MF (2001) Improvement in the mucoadhesive properties of alginate by the covalent attachment of cysteine. J Controlled Release 71: 277-285. doi: 10.1016/S0168-3659(01)00227-9
    [40] Jindal AB, Wasnik MN, Nair HA (2010) Synthesis of thiolated alginate and evaluation of mucoadhesiveness, cytotoxicity and release retardant properties. Indian J Pharm Sci 72: 766-774. doi: 10.4103/0250-474X.84590
    [41] Leone G, Torricelli P, Chiumiento A, et al. (2008) Amidic alginate hydrogel for nucleus pulposus replacement. J Biomed Mater Res A 84: 391-401.
    [42] Vallée F, Müller C, Durand A, et al. (2009) Synthesis and rheological properties of hydrogels based on amphiphilic alginate-amide derivatives. Carbohydr Res 344: 223-228. doi: 10.1016/j.carres.2008.10.029
    [43] Coates EE, Riggin CN, Fishe JP (2013) Photocrosslinked alginate with hyaluronic acid hydrogels as vehicles for mesenchymal stem cell encapsulation and chondrogenesis. J Biomed Mater Res A 101: 1962-1970.
    [44] Kumar MN, Muzzarelli RAA, Muzzarelli C, et al. (2004) Chitosan chemistry and pharmaceutical perspectives. Chem Rev 104: 6017-84. doi: 10.1021/cr030441b
    [45] Zhao Y, Park RD, Muzzarelli RAA (2010) Chitin Deacetylases: Properties and Applications. Mar Drugs 8: 24-46. doi: 10.3390/md8010024
    [46] Trzcinski S (2006) Combined degradation of chitosan. Polish Chitin Society Monograph XI, 103-11.
    [47] Varum KM, Ottoy MH, Smidsrød O (1994) Water solubility of partially N-acetylated chitosan as a function of pH: effect of chemical composition and depolymerization. Carbohydr Polyms 25: 65-70. doi: 10.1016/0144-8617(94)90140-6
    [48] Knaul JZ, Kasaai MR, Bui VT, et al. (1998) Characterization of deacetylated chitosan and chitosan molecular weight review. Can J Chem 76: 1699-1706.
    [49] Chattopadhyay DP, Inamdar MS (2010) Aqueous behavior of chitosan. Int Polym Science 2010 doi:10.1155/2010/939536.
    [50] Roberts GAF (1992) Chitin Chemistry. Houndmills UK: Macmillan Press.
    [51] An HK, Park BY, Kim DS (2001) Crab shell for the removal of heavy metals from aqueous solutions. Water Res 35: 3551-3556. doi: 10.1016/S0043-1354(01)00099-9
    [52] Wang QZ, Chen XG, Liu N, et al. (2006) Protonation constants of chitosan with different molecular weight and degree of deacetylation. Carbohydr Polym 65: 194-201. doi: 10.1016/j.carbpol.2006.01.001
    [53] Rinaudo M (2006) Chitin and chitosan: Properties and applications. Prog Polym Sci 31: 603-632. doi: 10.1016/j.progpolymsci.2006.06.001
    [54] Baxter A, Dillon M, Taylor KD, et al. (1992) Improved method for I.R. determination of the degree of N-acetylation of chitosan. Int J Biol Macromol 14: 166-169.
    [55] Muzzarelli RAA, Rochetti R (1985) Determination of the degree of acetylation of chitosans by first derivative ultraviolet spectrophotometry. Carbohydr Polym 5: 461-472. doi: 10.1016/0144-8617(85)90005-0
    [56] Vårum KM, Anthonsen MW, Grasdalen H, et al. (1991) Determination of the degree of N-acetylation and the distribution of N-acetyl groups in partially N-deacetylated chitins (chitosans) by high-field n.m.r. spectroscopy. Carbohydr Res 211:17-23. doi: 10.1016/0008-6215(91)84142-2
    [57] Värum KM, Anthonsen MW, Grasdalen H, et al. (1991) 13C-NMR studies of the acetylation sequences in partially N-deacetylated chitins (chitosans). Carbohydr Res 217: 19-27. doi: 10.1016/0008-6215(91)84113-S
    [58] Kasaai MR (2010) Determination of the degree of N-acetylation for chitin and chitosan by various NMR spectroscopy techniques: A review. Carbohydr Polym 79: 801-810. doi: 10.1016/j.carbpol.2009.10.051
    [59] Sreenivas SA, Pai KV (2008) ThiolatedChitosans: novel polymers for mucoadhesive drug delivery -A Review. Trop J Pharm Res 7: 1077-1088.
    [60] Jayakumar R, Nwe N, Tokura S, et al. (2007) Sulfated chitin and chitosan as novel biomaterials. Int J Biol Macromol 40: 175-181. doi: 10.1016/j.ijbiomac.2006.06.021
    [61] Sashiwa H, Kawasaki N, Nakayama A (2002) Synthesis of water-soluble chitosan derivatives by simple acetylation. Biomacromolecules 3: 1126-1128. doi: 10.1021/bm0200480
    [62] Jayakumar R, Reis RL, Mano JF (2006) Chemistry and Applications of Phosphorylated Chitin and Chitosan. e-Polymers 6: 447-462.
    [63] Jayakumar R, Nagahama H, Furuike T, et al. (2008) Synthesis of phosphorylated chitosan by novel method and its characterization. Int J Biol Macromol 42: 335-339. doi: 10.1016/j.ijbiomac.2007.12.011
    [64] Rúnarsson ÖV, Holappa J, Jónsdóttir S, et al. (2008) N-selective “one pot” synthesis of highly N-substituted trimethyl chitosan (TMC). Carbohydr Polym 74: 740-744. doi: 10.1016/j.carbpol.2008.03.008
    [65] Rosenthal R, Günzel D, Finger C, et al. (2012) The effect of chitosan on transcellular and paracellular mechanisms in the intestinal epithelial barrier. Biomaterials 33: 2791-2800. doi: 10.1016/j.biomaterials.2011.12.034
    [66] Muzzarelli RAA, Tanfani F, Emanuelli M, et al. (1982) N-(Carboxymethylidene) chitosans and N-(Carboxymethyl)-chitosans: Novel Chelating Polyampholytes obtained from Chitosan Glyoxylate. Carbohydr Res 107: 199-214. doi: 10.1016/S0008-6215(00)80539-X
    [67] Mourya VK, Inamdar NN, Tiwari A (2010) Carboxymethyl chitosan and its applications. Adv Mat Lett 1: 11-33. doi: 10.5185/amlett.2010.3108
    [68] George M, Abraham TE (2006) Polyionic Hydrocolloids forma the intestinal delivery of protein drugs: Alginate and chitosan-A review. J Controlled Release 114: 1-14. doi: 10.1016/j.jconrel.2006.04.017
    [69] Alves NM, Mano JF (2008) Chitosan derivatives obtained by chemical modification for biomedical and enviromental application. Int J Biol Macromol 43: 401-414. doi: 10.1016/j.ijbiomac.2008.09.007
    [70] Riva RL, Ragelle H, des Rieux A, et al. (2011) Chitosan and chitosan derivatives in drug delivery and tissue engineering. Adv Polym Sci 244: 19-44. doi: 10.1007/12_2011_137
    [71] Giri TK, Thakur A, Alexander A, et al. (2012) Modified chitosan hydrogels ad drug delivery and tissue engineering system: present status and application. Acta Pharm Sin B 2: 439-449. doi: 10.1016/j.apsb.2012.07.004
    [72] Berger J, Reist M, Mayer JM, et al. (2004) Structure and interactions in covalently and ionicallycrosslinked chitosan hydrogels for biomedical applications. Eur J Pharm Biopharm 57: 19-34. doi: 10.1016/S0939-6411(03)00161-9
    [73] Cai H, Zhang ZP, Sun PC, et al. (2005) Synthesis and characterization of thermo-and pH-sensitive hydrogels based on Chitosan-grafted N-isopropylacrylamide via γ-radiation. Rad Phys Chem 74: 26-30. doi: 10.1016/j.radphyschem.2004.10.007
    [74] El-Sherbiny IM, Smyth HDC (2010) Poly(ethylene glycol)-carboxymethyl chitosan-based pH-responsive hydrogels: photo-induced synthesis, characterization, swelling, and in vitro evaluation as potential drug carriers. Carbohydr Res 345: 2004-2012. doi: 10.1016/j.carres.2010.07.026
    [75] Yamada K, Chen T, Kumar G, et al. (2000) Chitosan Based Water-Resistant Adhesive. Analogy to Mussel Glue. Biomacromolecules 1: 252-8.
    [76] Il'ina AV, Varlamov VP (2005) Chitosan-based polyelectrolyte complexes: A review. Appl Biochem Micro 41: 5-11. doi: 10.1007/s10438-005-0002-z
    [77] Lu Y, Sun W, Gu Z (2014) Stimuli responsive nanomaterials for therapeutic protein delivery. J Controlled Release 194: 1-19. doi: 10.1016/j.jconrel.2014.08.015
    [78] Haug A, Larsen B, Smidsrød O (1963) The degradation of alginate at different pH values. Acta Chem Scand 17: 1466. doi: 10.3891/acta.chem.scand.17-1466
    [79] Timell TE (1964) The acid Hydrolysis of glycosides I. General conditions and the effect of the nature of the aglycone. Can J Chem 42: 1456-1472.
    [80] Haug A, Larsen B, Smidsrød O (1967) Alkaline degradation of alginate. Acta Chem Scand 21: 2859-2870. doi: 10.3891/acta.chem.scand.21-2859
    [81] Smidsrød O, Haug A, Larsen B (1967) Oxidative-reductive depolymerization: a note on the comparison of degradation rates of different polymers by viscosity measurements. Carbohydr Res 5: 482-485. doi: 10.1016/S0008-6215(00)81123-4
    [82] Holme HK, Foros H, Pettersen H, et al. (2001) Thermal depolymerization of chitosan chloride. Carbohydr Polym 46: 287-294. doi: 10.1016/S0144-8617(00)00332-5
    [83] Vårum KM, Ottøy MH, Smidsrød O (2001) Acid hydrolysis of chitosans. Carbohydr Polym 46: 89-98. doi: 10.1016/S0144-8617(00)00288-5
    [84] Menchicchi B, Fuenzalida JP, Bobbili KB, et al. (2014) Structure of chitosan determines its interactions with mucin. Biomacromolecules 15: 3550-3558. doi: 10.1021/bm5007954
    [85] Chen S, Cao Y, Ferguson LR, et al. (2013) Evaluation of mucoadhesive coatings of chitosan and thiolated chitosan for the colonic delivery of microencapsulated probiotic bacteria. J Microencapsu 30: 103-115. doi: 10.3109/02652048.2012.700959
    [86] Rubinstein A (2005) Colon drug delivery. Drug Discov Today: Technol 2: 33-37.
    [87] Vandamme TF, Lenourry A, Charrueau C, et al. (2002) The use of polysaccharides to target drugs to the colon. Carbohydr Polym 48: 219-231. doi: 10.1016/S0144-8617(01)00263-6
    [88] Wong TY, Preston LA, Schiller NL (2000) ALGINATE LYASE: Review of Major Sources and Enzyme Characteristics, Structure-Function Analysis, Biological Roles, and Applications. Ann Rev Microbiol 54: 289-340. doi: 10.1146/annurev.micro.54.1.289
    [89] Gacesa P (1988) Alginates. Carbohydr Polym 8: 161-182. doi: 10.1016/0144-8617(88)90001-X
    [90] Wargacki AJ, Leonard E, Win MN, et al. (2012) An Engineered Microbial Platform for Direct Biofuel Production from Brown Macroalgae. Science 335: 308-313. doi: 10.1126/science.1214547
    [91] Kean T, Thanou M (2010) Biodegradation, biodistribution and toxicity of chitosan. Adv Drug Deliv Rev 62: 3-11. doi: 10.1016/j.addr.2009.09.004
    [92] Funkhouser JD, Aronson NN (2007) Chitinase family GH18: evolutionary insights from the genomic history of a diverse protein family. BMC Evol Biol 7: 96. doi: 10.1186/1471-2148-7-96
    [93] Nordtveit RJ, Vårum KM, Smidsrød O (1994) Degradation of fully water-soluble, partially N-acetylated chitosans with lysozyme. Carbohydr Polym 23: 253-260. doi: 10.1016/0144-8617(94)90187-2
    [94] Brouwer J, van Leeuwen-Herberts T, Otting-van de Ruit M (1984) Determination of lysozyme in serum, urine, cerebrospinal fluid and feces by enzyme immunoassay. Clin Chim Acta 142: 21-30. doi: 10.1016/0009-8981(84)90097-4
    [95] Vårum KM, Myhr MM, Hjerde RJN, et al. (1997) In vitro degradation rates of partially N-acetylated chitosans in human serum. Carbohydr Res 299: 99-101. doi: 10.1016/S0008-6215(96)00332-1
    [96] Deckers D, Vanlint D, Callewaert L, et al. (2008) Role of the Lysozyme Inhibitor Ivy in Growth or Survival of Escherichia coli and Pseudomonas aeruginosa Bacteria in Hen Egg White and in Human Saliva and Breast Milk. Appl Environ Microbiol 74: 4434-4439. doi: 10.1128/AEM.00589-08
    [97] Callewaert L, Michiels CW (2010) Lysozyme in animal kingdom. J Biosci 35: 127-160. doi: 10.1007/s12038-010-0015-5
    [98] Cohen JS (1969) Proton Magnetic Resonance Studies of Human Lysozyme. Nature 223: 43-46. doi: 10.1038/223043a0
    [99] Kristiansen A, Vårum KM, Grasdalen H (1998) The interactions between highly de-N-acetylated chitosans and lysozyme from chicken egg white studied by 1H-NMR spectroscopy. Eur J Biochem 251: 335-342. doi: 10.1046/j.1432-1327.1998.2510335.x
    [100] Sasaki C, Kristiansen A, Fukamizo T, et al. (2003) Biospecific Fractionation of Chitosan. Biomacromolecules 4: 1686-1690. doi: 10.1021/bm034124q
    [101] Ren D, Yi H, Wang W, et al. (2005) The enzymatic degradation and swelling properties of chitosan matrices with different degrees of N-acetylaton. Carbohydr Res 340: 2403-2410. doi: 10.1016/j.carres.2005.07.022
    [102] Yang YM, Hu W, Wang XD, et al. (2007) The controlling biodegradation of chitosan fibers by n-acetylation in vitro and in vivo. J Mater Sci Mater Med 18: 2117-2121. doi: 10.1007/s10856-007-3013-x
    [103] Han T, Nwe N, Furuike T, et al. (2012) Methods of N-acetylated chitosan scaffolds and its in vitro biodegradation by lysozyme. J Biomed Sci Eng 5: 15-23. doi: 10.4236/jbise.2012.51003
    [104] Vårum KM, Holme HK, Izume M, et al. (1996) Determination of enzymatic hydrolysis specificity of partially N-acetylated chitosans. Biochem Biophy Acta (BBA) 1291: 5-15. doi: 10.1016/0304-4165(96)00038-4
    [105] Wen X, Kellum JA (2012) N-Acetyl-beta-D-Glucosaminidase (NAG). Encyclopedia Intensive Care Medicine 1509-1510.
    [106] Lim SM, Song DK, Oh SH, et al. (2008) In vitro and in vivo degradation behavior of acetylated chitosan porous beads. J Biomater Sci Polym Ed 19: 453-466.
    [107] Bajaj P, Schweller RM, Khademhosseini A, et al. (2014) 3D Biofabrication Strategies for Tissue Engineering and Regenerative Medicine. Annu Rev Biomed Eng 16: 247-276. doi: 10.1146/annurev-bioeng-071813-105155
    [108] Guarino V, Cirillo V, Altobelli R, et al. (2015) Polymer-based platforms by electric field-assisted techniques for tissue engineering and cancer therapy. Expert Rev Med Devices 12: 113-29. doi: 10.1586/17434440.2014.953058
    [109] Li Z, Zhang M (2005) Chitosan-alginate as scaffolding material for cartilage tissue engineering. J Biomed Mater Res A 75: 485-493.
    [110] Phan-Lai V, Florczyk SJ, Kievit FM (2013) Three-Dimensional Scaffolds to Evaluate Tumor Associated Fibroblast-Mediated Suppression of Breast Tumor Specific T Cells. Biomacromolecules 14: 1330-1337. doi: 10.1021/bm301928u
    [111] Florczyk SJ, Liu G, Kievit FM, et al. (2012) 3D porous chitosan-alginate scaffolds: a new matrix for studying prostate cancer cell-lymphocyte interactions in vitro. Adv Healthc Mater 1: 590-599. doi: 10.1002/adhm.201100054
    [112] Kievit FM Florczyk SJ, Leung MC, et al. (2010) Chitosan-alginate 3D scaffolds as a mimic of the glioma tumor microenvironment. Biomaterials 31: 5903-5910. doi: 10.1016/j.biomaterials.2010.03.062
    [113] Mura S, Nicolas J, Couvreur P (2013) Stimuli-Responsive Nanocarriers for Drug Delivery. Nat Mater 12: 991-1003. doi: 10.1038/nmat3776
    [114] Gonçalves M, Figueira P, Maciel D (2014) pH-sensitive Laponite®/doxorubicin/alginate nanohybrids with improved anticancer efficacy. Acta Biomater 10: 300-307 doi: 10.1016/j.actbio.2013.09.013
    [115] Kim CK, Lee EJ (1992) The controlled release of blue dextran from alginate beads. Int J Pharm 79: 11-19. doi: 10.1016/0378-5173(92)90088-J
    [116] Gulbake A, Jain SK (2012) Chitosan: a potential polymer for colon-specific drug delivery system. Exp Opin Drug Deliv 9: 713-729. doi: 10.1517/17425247.2012.682148
    [117] Ganguly K, Aminabhavi TM, Kulkarni AR (2011) Colon Targeting of 5-Fluorouracil Using Polyethylene Glycol Cross-linked Chitosan Microspheres Enteric Coated with Cellulose Acetate Phthalate. Ind Eng Chem Res 50: 11797-11807. doi: 10.1021/ie201623d
    [118] Lai CK, Lu YL, Hsieh JT, et al. (2014), Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending toxin for gastric cancer therapy. Nanomedicine 9: 803-817.
    [119] Arora S, Budhiraja RD (2012) Chitosan-alginate microcapsules of amoxicillin for gastric stability and mucoadhesion. J Adv Pharm Techno Res 3: 68-74.
    [120] Du J, Dai J, Liu JL, et al. (2006) Novel pH-sensitive polyelectrolyte carboxymethyl Konjac glucomannan-chitosan beads as drug carriers. React Funct Polym 66: 1055-1061. doi: 10.1016/j.reactfunctpolym.2006.01.014
    [121] Liu Z, Jiao Y, Liu F, et al. (2007) Heparin/chitosan nanoparticle carriers prepared by polyelectrolyte complexation. J Biomed Mater Res Part A 83: 806-812.
    [122] Zhou T, Xiao C, Fan J, et al. (2012) A nanogel of on-site tunable pH-response for efficient anticancer drug delivery. Acta Biomater 9: 4546-4557.
    [123] Kutlu C, Çakmak AS, Gümüşderelioğlu M (2014) Double-effective chitosan scaffold-PLGA nanoparticle system for brain tumour therapy: in vitro study. J Microencapsul 31: 700-707. doi: 10.3109/02652048.2014.913727
    [124] Feng C, Song R, Sun G, et al. (2014) Immobilization of Coacervate Microcapsules in Multilayer Sodium Alginate Beads for Efficient Oral Anticancer Drug Delivery. Biomacromolecules15: 985-996.
    [125] Anchisi C, Meloni MC, Maccioni AM (2006) Chitosan beads loaded with essential oils in cosmetic formulations. J Cosmet Sci 57: 205-214.
    [126] Ariza-Avidad M, Nieto A, Salinas-Castillo A, et al. (2014) Monitoring of degradation of porous silicon photonic crystals using digital photograph. Nanoscale Res Lett 9: 410. doi: 10.1186/1556-276X-9-410
    [127] Jung SM, Yoon GH, Lee HC, et al. (2015) Chitosan nanoparticle/PCL nanofiber composite for wound dressing and drug delivery. J Biomater Sci Polym 26: 252-263. doi: 10.1080/09205063.2014.996699
    [128] Badawy ME, El-Aswad AF (2014) Bioactive paper sensor based on the acetylcholinesterase for the rapid detection of organophosphate and carbamate pesticides. Int J Anal Chem 2014 Article ID 536823.
    [129] Spreen KA, Zikakis JP, Austin PR (1984) Chitin, Chitosan and Related Enzymes. In J P Zikakis (Ed.) Academic Press, Orlando, 57.
    [130] Vázquez N, Chacón M, Meana Á, et al. (2015) Keratin-chitosan membranes as scaffold for tissue engineering of human cornea. Histol Histopathol 30: 813-821.
    [131] Cheng YH, Hung KH, Tsai TH, et al. (2014) Sustained delivery of latanoprost by thermosensitive chitosan-gelatin-based hydrogel for controlling ocular hypertension. Acta Biomater 10: 4360-4366. doi: 10.1016/j.actbio.2014.05.031
    [132] Wu FC, Tseng RL, Juang RS (2010) A review and experimental verification of using chitosan and its derivatives as adsorbents for selected heavy metals. J Environ Manage 91: 798-806. doi: 10.1016/j.jenvman.2009.10.018
    [133] Szymańska E, Winnicka K, AmelianA, et al. (2014) Vaginal chitosan tablets with clotrimazole-design and evaluation of mucoadhesive properties using porcine vaginal mucosa, mucin and gelatin. Chem Pharm Bull (Tokyo) 62:160-167. doi: 10.1248/cpb.c13-00689
    [134] Rao TV, Kumar GK, Ahmed MG, et al. (2012) Development and evaluation of chitosan based oral controlled matrix tablets of losartan potassium. Int J Pharm Investig 2: 157-161. doi: 10.4103/2230-973X.104399
    [135] Wassmer S, Rafat M, Fong WG, et al. (2013) Chitosan microparticles for delivery of proteins to the retina. Acta Biomater 9: 7855-7864. doi: 10.1016/j.actbio.2013.04.025
    [136] Chen CK, Wang Q, Jones CH, et al. (2014) Synthesis of pH-responsive chitosan nanocapsules for the controlled delivery of doxorubicin. Langmuir 30: 4111-4119. doi: 10.1021/la4040485
    [137] Prasad M, Palanivelu P (2014) Immobilization of a thermostable, fungal recombinant chitinase on biocompatible chitosan beads and the properties of the immobilized enzyme. Biotechnol Appl Biochem 62: 523-529.
    [138] Jain SK, Chourasia MK, Sabitha M, et al. (2003) Development and characterization of transdermal drug delivery systems for diltiazem hydrochloride. Drug Deliv 10: 169-177. doi: 10.1080/713840400
    [139] Kong M, Chen XG, Xing K, et al. (2010) Antimicrobial properties of chitosan and mode of action: a state of the art review. Int J Food Microbiol 144: 51-63. doi: 10.1016/j.ijfoodmicro.2010.09.012
    [140] Yang J, Luo K, Li D, et al. (2013) Preparation, characterization and in vitro anticoagulant activity of highly sulfated chitosan. Int J Biol Macromol 52: 25-31. doi: 10.1016/j.ijbiomac.2012.09.027
    [141] Whang HS, Kirsch W, Zhu YH, et al. (2005) Hemostatic Agents Derived from Chitin and Chitosan. J Macromol Sci Part C: Polym Rev 45: 309-323. doi: 10.1080/15321790500304122
    [142] Čopíková J, Taubner T, Tůma J, et al. (2015) Cholesterol and fat lowering with hydrophobic polysaccharide derivatives. Carbohydr Polym 116: 207-214. doi: 10.1016/j.carbpol.2014.05.009
    [143] Pereira GG, Guterres SS, Balducci AG, et al. (2014) Polymeric films loaded with vitamin E and aloe vera for topical application in the treatment of burn wounds. Biomed Res Int 2014 ID 641590.
    [144] Rojas-Graü MA, Tapia MS, Rodríguez FJ, et al. (2007) Alginate and gellan based edible coatings as support of antibrowning agents applied on fresh-cut Fuji apple. Food Hydrocolloids 21: 118-127. doi: 10.1016/j.foodhyd.2006.03.001
    [145] Wargacki AJ, Leonard E, Win MN, et al. (2012) An engineered microbial platform for direct biofuel production from brown macroalgae. Science 335: 308-313. doi: 10.1126/science.1214547
    [146] Sarei F, Dounighi NM, Zolfagharian H, et al. (2013) Alginate Nanoparticles as a Promising Adjuvant and Vaccine Delivery System. Indian J Pharm Sci 75: 442-449. doi: 10.4103/0250-474X.119829
    [147] Tønnesen HH, Karlsen J (2002) Alginate in Drug Delivery Systems. Drug Dev Ind Pharm 28: 621-630. doi: 10.1081/DDC-120003853
    [148] Giri TK, Thakur D, Alexander A, et al. (2012) Alginate based Hydrogel as a Potential Biopolymeric Carrier for Drug Delivery and Cell Delivery Systems: Present Status and Applications. Curr Drug Deliv 9: 539-555. doi: 10.2174/156720112803529800
    [149] Murata Y, Sasaki N, Miyamoto E, et al. (2000) Use of floating alginate gel beads for stomach-specific drug deliver. Eur J Pharm Biopharm 50: 221-226. doi: 10.1016/S0939-6411(00)00110-7
    [150] Paul W, Sharma CP (2004) Chitosan and Alginate Wound Dressings: A Short Review. Trends Biomater Artif Organs 18: 18-23.
    [151] Tanga M, Chena W, Weira MD, et al. (2012) Human embryonic stem cell encapsulation in alginate microbeads in macroporous calcium phosphate cement for bone tissue engineering. Acta Biomater 8: 3436-3445. doi: 10.1016/j.actbio.2012.05.016
    [152] Martinez JC, Kim JW, Ye C, et al. (2012) A Microfluidic Approach to Encapsulate Living Cells in Uniform Alginate Hydrogel Microparticles. Macromol Biosci 12:946-951. doi: 10.1002/mabi.201100351
    [153] Yang Q, Lei S (2014) Alginate Dressing Application in Hemostasis After Using Seldinger Peripherally Inserted Central Venous Catheter in Tumor Patients. Indian J Hematol Blood Transfus DOI 10.1007/s12288-014-0490-1.
    [154] Kimura Y, Watanabe K, Okuda H (1996) Effects of soluble sodium alginate on cholesterol excretion and glucose tolerance in rats. J Ethnopharmacol 54: 47-54. doi: 10.1016/0378-8741(96)01449-3
    [155] Ueno M, Tamura Y, Toda N, et al. (2012) Sodium Alginate Oligosaccharides Attenuate Hypertension in Spontaneously Hypertensive Rats Fed a Low-Salt Diet. Clin Exp Hypertens 34: 305-310. doi: 10.3109/10641963.2011.577484
    [156] Odunsi ST, Vázquez-Roque MI, Camilleri M (2009) Effect of alginate on satiation, appetite, gastric function, and selected gut satiety hormones in overweight and obesity. Obesity 18: 1579-1584.
    [157] Bhunchu S, Rojsitthisak P (2014) Biopolymeric alginate-chitosan nanoparticles as drug delivery carriers for cancer therapy. Pharmazie 69: 563-570.
    [158] Idota Y, Harada H, Tomono T, et al. (2013) Alginate Enhances Excretion and Reduces Absorption of Strontium and Cesium in Rats. Biol Pharm Bull 36: 485-491. doi: 10.1248/bpb.b12-00899
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