Advertisement

Advances in Biomedical Application of Chitosan and Its Functionalized Nano-derivatives

  • Jobina Rajkumari
  • Siddhardha BusiEmail author
Chapter

Abstract

The recent advances in nanotechnology open new avenues for the development of functionalized nanomaterials with wide potential application. Chitosan has become one of the most promising biopolymers with wide application in diagnostics and therapeutics. It is a linear copolymer of β-(1–4)-linked 2-acetamido-2-deoxy-β-d-glucopyranose and 2-amino-2-deoxy-β-d-glycopyranose, with a varying content of N-acetyl groups. It is obtained by deacetylation of parent polymer, chitin, and also occurs naturally in fungal species such as Absidia glauca, Absidia coerulea, Aspergillus niger, Mucor rouxii, Gongronella butleri, Phycomyces blakesleeanus, Absidia blakesleeanus, Rhizopus oryzae, Trichoderma reesei, and Lentinus edodes. Chitosan can also be directly extracted from fungi by alkaline/acid treatment and by use of microorganisms/proteolytic enzymes. Unlike chitin, chitosan is readily soluble in dilute acetic acid and widely used in preparation of gels, films, and fibers. The production of the biopolymer is generally influenced by parameters such as the nutritional factors, mode of cultivation, temperature, pH, and mineral salts. In therapeutics, chitosan and chitosan-based materials are used as antimicrobial, antitumor, antiulcer, antidiabetic, and a cholesterol-lowering agent. Being a naturally occurring polysaccharide, chitosan and its functionalized derivatives exhibit unique properties, such as biocompatibility, biodegradability, biological activity, and low toxicity. The conformational flexibility of chitosan is attributed to the presence of the free primary amino groups which makes chitosan an ideal candidate for biofabrication. Various methods, such as ionic gelation, desolvation, spray-drying, and covalent cross-linking, have been employed for functionalization of chitosan. Nanoparticles and its biofabrication impart desirable functional characteristics to chitosan. The molecular weight and the concentration of chitosan used along with an amount of cross-linking govern the physical properties of chitosan nanoparticles formed. Chitosan nanocomposites have shown to improve the dissolution rate of poorly soluble drugs and, thus, are exploited for enhancement of drug bioavailability and delivery. Various therapeutic agents, such as anticancer, anti-inflammatory, antibiotics, antithrombotic, steroids, proteins, amino acids, antidiabetic, and diuretics, have been incorporated in chitosan nanocomposites. The controlled release of therapeutic agents opened new windows in drug delivery and bio-imaging techniques using chitosan. Hence, chitosan and its nano-derivatives serve as one of the sustainable and ecofriendly alternative to synthetic polymers in biomedical applications.

Keywords

Chitosan Drug delivery Peptide Antimicrobial Emulsions Antibiotics 

References

  1. Agnihotri SA, Aminabhavi TM (2004) Controlled release of clozapine through chitosan microparticles prepared by a novel method. J Control Release 96:245–259CrossRefPubMedGoogle Scholar
  2. Agnihotri SA, Mallikarjuna NN, Aminabhavi TM (2004) Recent advances on chitosan-based micro- and nanoparticles in drug delivery. J Control Release 100(1):5–28CrossRefPubMedGoogle Scholar
  3. Akila RM (2014) Fermentative production of fungal Chitosan, a versatile biopolymer (perspectives and its applications). Adv Appl Sci Res 5(4):157–170Google Scholar
  4. Aranaz I, Harris R, Navarro-Garcia F, Heras A, Acosta N (2016) Chitosan based films as supports for dual antimicrobial release. Carbohydr Polym 146:402–410CrossRefPubMedGoogle Scholar
  5. Bowman SM, Free SJ (2008) The structure and synthesis of the fungal cell wall. Bioassays 28(8):799–808CrossRefGoogle Scholar
  6. Bugnicourt L, Ladaviere C (2016) Interests of chitosan nanoparticles ionically cross-linked with tripolyphosphate for biomedical applications. Prog Polym Sci 60:1–17CrossRefGoogle Scholar
  7. Chatterjee S, Adhya M, Guha KA, Chatterjee BP (2005) Chitosan from Mucor rouxii: production and physico-chemical characterization. Process Biochem 40:395–400CrossRefGoogle Scholar
  8. Chattopadhyay D, Inamdar M (2013) Improvement in properties of cotton fabric through synthesized nano-chitosan application. Indian J Fibre Text Res 38:14–21Google Scholar
  9. Cheung RC, Ng TB, Wong JH, Chan WY (2015) Chitosan: an update on potential biomedical and pharmaceutical applications. Mar Drugs 13(8):5156–5186CrossRefPubMedPubMedCentralGoogle Scholar
  10. Dash M, Chiellini F, Ottenbrite RM, Chiellini E (2011) Chitosan-a versatile semi-synthetic polymer in biomedical applications. Prog Polym Sci 36:981–1014CrossRefGoogle Scholar
  11. Del Guidice G, Baudner B (2015) Mucosal vaccines with chitosan adjuvant and meningococcal antigens. PatentGoogle Scholar
  12. Dhillon GS, Kaur S, Brar SK (2014) Facile fabrication and characterization of chitosan-based zinc oxide nanoparticles and evaluation of their antimicrobial and antibiofilm activity. Int Nano Lett 4:107CrossRefGoogle Scholar
  13. Di Mario F, Rapana P, Tomati U, Galli E (2008) Chitin and chitosan from Basidiomycetes. Int J Biol Macromol 43(1):8–12CrossRefPubMedGoogle Scholar
  14. Du WL, Niu SS, Xu YL, Xu ZR, Fan CL (2009) Antibacterial activity of chitosan tripolyphosphate nanoparticles loaded with various metal ions. Carbohydr Polymer 75:385–389CrossRefGoogle Scholar
  15. Duttagupta DS, Jadhav VM, Kadam VJ (2015) Chitosan: a propitious biopolymer for drug delivery. Curr Drug Deliv 12(4):369–381CrossRefPubMedGoogle Scholar
  16. He P, Davis SS, Illum L (1999) Chitosan microspheres prepared by spray drying. Int J Pharm 187:53–65CrossRefPubMedGoogle Scholar
  17. Hebeish AA, Ramadan MA, Montaser AS, Farag AM (2014) Preparation, characterization and antibacterial activity of chitosan-g-poly acrylonitrile/silver nanocomposite. Int J Biol Macromol 68:178–184CrossRefPubMedGoogle Scholar
  18. Hejazi R, Amiji M (2002) Stomach-specific anti-H pylori therapy. I: preparation and characterization of tetracyline-loaded chitosan microspheres. Int J Pharm 235:87–94CrossRefPubMedGoogle Scholar
  19. Huang Y, Yeh M, Chiang C (2002) Formulation factors in preparing BTM-chitosan microspheres by spray drying method. Int J Pharm 242:239–242CrossRefPubMedGoogle Scholar
  20. Huang HY, Shieh YT, Shih CM, Twu YK (2010) Magnetic chitosan/iron (II, III) oxide nanoparticles prepared by spray-drying. Carbohydr Polym 81(4):906–910CrossRefGoogle Scholar
  21. Ibrahim HM, El-Bisi MK, Taha GM, El-Alfy EA (2015) Chitosan nanoparticles loaded antibiotics as drug delivery bio material. J Appl Pharm Sci 5(10):085–090CrossRefGoogle Scholar
  22. Ichikawa H, Uneme T, Andoh T, Arita Y, Fujimoto T, Suzuki M, Sakurai Y, Shinto H, Fukasawa T, Fujii F, Fukumori Y (2014) Gadolinium-loaded chitosan nanoparticles for neutron-capture therapy: influence of micrometric properties of the nanoparticles on tumor-killing effect. Appl Radiat Isot 88:109–113CrossRefPubMedGoogle Scholar
  23. Jahanbin TH, Sauriat-Dorizon P, Spearman S, Benderbous H, Korri-Youssoufi (2015) Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast agents for magnetic resonance imaging. Mater Sci Eng C 52:325–332CrossRefGoogle Scholar
  24. Jamil B, Habib H, Abbasi S, Nasir H, Rahman A, Rehman A, Bokhari H, Imran M (2016) Cefazolin loaded chitosan nanoparticles to cure multi drug resistant Gram-negative pathogens. Carbohydr Polym 20(136):682–691CrossRefGoogle Scholar
  25. Jayakumar R, Menon D, Manzoor K, Nair SV, Tamura H (2010) Biomedical applications of chitin and chitosan based nanomaterials-a short review. Carbohydr Polym 82:227–232CrossRefGoogle Scholar
  26. Kleekayai T, Suntornsuk W (2011) Production and characterization of chitosan obtained from Rhizopus oryzae grown on potato chip processing waste. World J Microbiol Biotechnol 27(5):1145–1154CrossRefGoogle Scholar
  27. Kong M, Chen XG, Xing K, Park HJ (2010) Antimicrobial properties of chitosan and mode of action: a state of the art review. Int J Food Microbiol 144:51–63CrossRefPubMedGoogle Scholar
  28. Kuhlmann KA, Czupala J, Haunhorst Weiss T, Prasch U, Schorken A (2000) Preparation and characterization of chitosan from Mucorales. In: Peter M, Domard A, Muzzarelli RAA (eds) Advances in chitin science. Druckhaus Schmergow, Germany, pp 7–14Google Scholar
  29. Kumbar SG, Kulkarni AR, Aminabhavi TM (2002) Crosslinked chitosan microspheres for encapsulation of diclofenac sodium: effect of crosslinking agent. J Microencapsul 19:173–180CrossRefPubMedGoogle Scholar
  30. Leong YS, Candau F (1982) Inverse microemulsion polymerization. J Phys Chem 86:2269–2271CrossRefGoogle Scholar
  31. Liu Y, Jia SY, Wu QA, Ran JY, Zhang W, Wu SH (2011) Studies of Fe3O4-chitosan nanoparticles prepared by co-precipitation under the magnetic field for lipase immobilization. Catal Commun 12:717CrossRefGoogle Scholar
  32. Liu L, Dong X, Zhu D, Song L, Zhang H, Leng XG (2014) TATLHRH conjugated low molecular weight chitosan as a gene carrier specific for hepatocellular carcinoma cells. Int J Nanomedicine 9:2879CrossRefPubMedPubMedCentralGoogle Scholar
  33. Lu Y, Cheng D, Lu S, Huang F, Li G (2014) Preparation of quaternary ammonium salt of chitosan nanoparticles and their textile properties on Antheraea pernyi silk modification. Text Res J 84(19):2115–2124CrossRefGoogle Scholar
  34. Madureira AR, Pereira A, Pintado M (2015) Current state on the development of nanoparticles for use against bacterial gastrointestinal pathogens. Focus on chitosan nanoparticles loaded with phenolic compounds. Carbohydr Polymer 130:429–439CrossRefGoogle Scholar
  35. Majithiya RJ, Murthy RS (2005) Chitosan-based mucoadhesive microspheres of clarithromycin as a delivery system for antibiotic to stomach. Curr Drug Deliv 2(3):235–242CrossRefPubMedGoogle Scholar
  36. Mao HQ, Roy K, Troung-Le VL, Janes KA, Lin KY, Wang Y, August JT, Leong KW (2001) Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J Control Release 70:399–421CrossRefPubMedGoogle Scholar
  37. Mazancova P, Nemethova V, Lacik I, Razga F (2017) Chitosan-based particles: the (forgotten) interplay between process, properties and performance. Mater Sci Eng C Mater Biol Appl 71:570–571CrossRefPubMedGoogle Scholar
  38. Mitra A, Dey B (2011) Chitosan microspheres in novel drug delivery systems. Indian J Pharm Sci 73(4):355–366PubMedPubMedCentralGoogle Scholar
  39. Mitra S, Gaur U, Ghosh PC, Maitra AN (2001) Tumor targeted delivery of encapsulated dextran-doxorubicin conjugate using chitosan nanoparticles as carrier. J Control Release 74:317–323CrossRefPubMedGoogle Scholar
  40. Muzzarelli RAA, Boudrant J, Meyer D, Manno N, DeMarchis M, Paoletti MG (2012) Current views on fungal chitin/chitosan, human chitinases, food preservation, glucans, pectins and inulin: a tribute to Henri Braconnot, precursor of the carbohydrate polymers science, on the chitin bicentennial. Carbohydr Polymer 87:995–1012CrossRefGoogle Scholar
  41. Niederhofer A, Muller BW (2004) A method for direct preparation of chitosan with low molecular weight from fungi. Eur J Pharm Biopharm 57(1):101–105CrossRefPubMedGoogle Scholar
  42. Piras AM, Maisetta G, Sandreschi S, Esin S, Gazzarri M, Batoni G, Chiellini F (2014) Preparation, physical-chemical and biological characterization of chitosan nanoparticles loaded with lysozyme. Int J Biol Macromol 67:124–131CrossRefPubMedGoogle Scholar
  43. Piras AM, Maisetta G, Sandreschi S, Gazzarri M, Bartoli C, Grassi L, Esin S, Chiellini F, Batoni G (2015) Chitosan nanoparticles loaded with the antimicrobial peptide temporin B exert a long-term antibacterial activity in vitro against clinical isolates of Staphylococcus epidermidis. Front Microbiol 6:372CrossRefPubMedPubMedCentralGoogle Scholar
  44. Pochanavanich P, Suntornsuk W (2002) Fungal chitosan production and its characterization. Lett Appl Microbiol 35(1):17–21CrossRefPubMedGoogle Scholar
  45. Potara M, Jakab E, Damert A, Popescu O, Canpean V, Astilean S (2011) Synergistic antibacterial activity of chitosan-silver nanocomposites on Staphylococcus aureus. Nanotechnology 22(13):135101CrossRefPubMedGoogle Scholar
  46. Qi L, Xu Z, Jiang X, Li Y, Wang M (2005) Cytotoxic activities of chitosan nanoparticles and copper-loaded nanoparticles. Bioorg Med Chem Lett 15(5):1397–1399CrossRefPubMedGoogle Scholar
  47. Qu J, Liu G, Wang Y, Hong R (2010) Preparation of Fe3O4-chitosan nanoparticles used for hyperthermia. Adv Powder Technol 21(4):461–467CrossRefGoogle Scholar
  48. Ragelle H, Riva R, Vandermeulen G, Naeye B, Pourcelle V, Le Duff CS, D’Haese C, Nysten B, Braeckmans K, De Smedt SC (2014) Chitosan nanoparticles for siRNA delivery: optimizing formulation to increase stability and efficiency. J Control Release 176:54–63CrossRefPubMedGoogle Scholar
  49. Sanjai C, Kothan S, Gonil P, Saesoo S, Sajomsang W (2014) Chitosan-triphosphate nanoparticles for encapsulation of super-paramagnetic iron oxide as an MRI contrast agent. Carbohydr Polym 104:231–237CrossRefPubMedGoogle Scholar
  50. Sankar C, Rani M, Srivastava AK, Mishra B (2001) Chitosan based pentazocine microspheres for intranasal systemic delivery: development and biopharmaceutical evaluation. Pharmazie 56:223–226PubMedGoogle Scholar
  51. Sawaengsak C, Mori Y, Yamanishi K, Mitrevej A, Sinchaipanid N (2014) Chitosan nanoparticle encapsulated hemagglutinin-split influenza virus mucosal vaccine. AAPS Pharm SciTech 15(2):317–325CrossRefGoogle Scholar
  52. Shi LE, Fang XJ, Xing LY, Chen M, Zhu DS, Zhu L, Guo XF, Zhao LM, Tang ZX (2011) Chitosan nanoparticles as drug delivery carriers for biomedical engineering. J Chem Soc Pak 33:929–934Google Scholar
  53. Shikata F, Tokumitsu H, Ichikawa H, Fukumori Y (2001) In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer. Eur J Pharm Biopharm 53(1):57–63CrossRefGoogle Scholar
  54. Shrestha A, Hamblin MR, Kishen A (2014) Photoactivated rose bengal functionalized chitosan nanoparticles produce antibacterial/biofilm activity and stabilize dentin-collagen. Nanomedicine 10(3):491–501CrossRefPubMedGoogle Scholar
  55. Suntornsuk W, Pochanakanich P, Suntornsuk L (2002) Fungal chitosan production on food processing by-products. Process Biochem 37:727–729CrossRefGoogle Scholar
  56. Tajdini F, Amini MA, Nafissi-Varcheh N, Faramarzi MA (2010) Production, physiochemical and antimicrobial properties of fungal chitosan from Rhizomucor miehei and Mucor racemosus. Int J Biol Macromol 47(2):180–183CrossRefPubMedGoogle Scholar
  57. Tayel AA, Moussa S, Opwis K, Knittel D, Schollmeyer E, Nickisch-Hartfiel A (2010) Inhibition of microbial pathogens by fungal chitosan. Int J Biol Macromol 47(1):10–14CrossRefPubMedGoogle Scholar
  58. Tayel AA, Moussa SH, El-Tras WF, Elguindy NM, Opwis K (2011) Antimicrobial textile treated with chitosan from Aspergillus niger mycelial waste. Int J Biol Macromol 49(2):241–245CrossRefPubMedGoogle Scholar
  59. Tokumitsu H, Ichikawa H, Fukumori Y (1999) Chitosan-gadopentetic acid complex nanoparticles for gadolinium neutron-capture therapy of cancer: preparation by novel emulsion-droplet coalescence technique and characterization. Pharm Res 16:1830–1835CrossRefPubMedGoogle Scholar
  60. Wang JJ, Zeng ZW, Xiao RZ, Xie T, Zhou GL, Zhan XR, Wang SL (2011) Recent advances of chitosan nanoparticles as drug carriers. Int J Nanomedicine 6:765–774PubMedPubMedCentralGoogle Scholar
  61. Wu T, Wu C, Fu S, Wang L, Yuan C, Chen S, Hu Y (2017) Integration of lysozyme into chitosan nanoparticles for improving antibacterial activity. Carbohydr Polym 155:192–200CrossRefPubMedGoogle Scholar
  62. Xu Y, Du Y (2003) Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int J Pharm 250:215–226CrossRefPubMedGoogle Scholar
  63. Younes I, Rinaudo M (2015) Chitin and chitosan preparation from marine sources. Structure, properties and applications. Mar Drugs 13(3):1133–1174CrossRefPubMedPubMedCentralGoogle Scholar
  64. Yuan S, Yin J, Jiang W, Liang B (2013) Enhancing antibacterial activity of surface-grafted chitosan with immobilized lysozyme on bioinspired stainless steel substrates. Colloids Surf B Biointerf 106:11–21CrossRefGoogle Scholar
  65. Zhang HC, Zhao YY (2015) β-Chitosan nanoparticles encapsulated tea polyphenol–Zn complex as a potential antioxidant substances delivery carrier. Food Hydrocoll 48:260–273CrossRefGoogle Scholar
  66. Zhang J, Xia W, Liu P, Cheng Q, Tahirou T, Gu W, Li B (2010) Chitosan modification and pharmaceutical/biomedical applications. Mar Drugs 8(7):1962–1987CrossRefPubMedPubMedCentralGoogle Scholar
  67. Zhang H, Jung J, Zhao Y (2016) Preparation, characterization and evaluation of antibacterial activity of catechins and catechins-Zn complex loaded β-chitosan nanoparticles of different particle sizes. Carbohydr Polym 137:82–91CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of Microbiology, School of Life SciencesPondicherry UniversityPuducherryIndia

Personalised recommendations