Dextran Graft Copolymers: Synthesis, Properties and Applications

Chapter

Abstract

A graft polymer of methyl methacrylate (MMA) on dextran was prepared using ceric ammonium nitrate (CAN). The properties of these graft copolymers are very interesting because of their amphiphilic microseparated domain. The solubility, infrared absorption spectrum and thermal behavior of the graft copolymer were investigated. It was found that an extruded film of the copolymer not only shows better water wettability and water absorbing power than PMMA but also exhibits thrombo-resistance and can be formed into a transparent contact lens with an affinity for tears and blood. A transparent dextran-matrix copolymer (DMC) has also been newly prepared that consists of a polyelectrolyte complex between cationic dextran and unsaturated acids with compounds of vinyl. This material has been used for hard contact lenses and intraocular lenses. A stable latex of 2-diethylaminoethyl (DEAE)-dextran-MMA graft copolymer (DDMC) has been developed for non-viral gene delivery vectors that are autoclavable at 121 °C for 15 min. Transfection activity was determined using the X-gal staining method, and DDMC samples showed at least 5–10 times higher transfection activity than the starting DEAE-dextran hydrochloride. DDMC has been also confirmed as having a high facility for protection against DNase degradation. The resistance of B16F10 melanoma cells to paclitaxel was confirmed using survival curve analysis. A DDMC/paclitaxel complex showed superior anticancer activity to paclitaxel alone. The rate of mortality of the cells was determined using Michaelis–Menten equations, as the complex promoted an allosteric supramolecular reaction to tubulin. Our results show that the DDMC/paclitaxel complex was not extensively degraded in cells and achieved good efficacy as an intact supramolecular anticancer agent.

Keywords

Dextran Contact lens MMA Matrix copolymer Non-viral gene delivery Transfection DNA Intracellular transport Cancer Drug delivery systems (DDS) Supramolecular facilities Melanoma cells Nanoparticles DEAE-dextran-MMA copolymer/paclitaxel complex Cancer Paclitaxel Graft copolymer DEAE-dextran 

Notes

Acknowledgements

This study is very thankful to the late Dr. Sadayoshi Kamia, professor emeritus of Nara Medical University, for his study of the Bio-Plastics and to the late Dr. George Butler, professor emeritus of University of Florida, for his encouragement and the education we received.

References

  1. 1.
    Mino G, Kaizerman K (1958) Polymerization initiated by ceric ion redox systems. J Polym Sci 31:242–243CrossRefGoogle Scholar
  2. 2.
    Ite F, Takayama Y (1961) Graft polymerization of MMA onto cellulose. J Chem Soc Jpn Ind Chem Sect [Kogyo Kagaku Zasshi] 64:213–218Google Scholar
  3. 3.
    Nishiuchi T, Okazaki K (1972) Graft copolymerization of methyl methacrylate onto starch and triethylamino starch. J Chem Soc Jpn Ind Chem Sect [Nippon Kagaku Zasshi] 1972:1728–1734Google Scholar
  4. 4.
    Nishiuchi T, Okazaki K (1970) Graft copolymerization of methyl methacrylate onto carboxymethyl-cellulose. J Chem Soc Jpn Ind Chem Sect [Kogyo Kagaku Zasshi] 73:2699–2703Google Scholar
  5. 5.
    Wallace RA, Yong DG (1966) Graft polymerization kinetics of acrylamide initiated by ceric nitrate-dextran redox systems. J Polym Sci Polym Chem Ed A-1 1:1179–1190CrossRefGoogle Scholar
  6. 6.
    Imai Y (1972) Anti-thrombogenic materials—role of heterogeneous surface microstructure. Kobunshi 21:569–573CrossRefGoogle Scholar
  7. 7.
    Onishi Y, Maruno S, Kamiya S, Hokkoku S, Hasegawa M (1978) Preparation and characteristics of dextran-methyl methacrylate graft copolymer. Polymer 19:1325–1328CrossRefGoogle Scholar
  8. 8.
    Onishi Y (1980) Effects of dextran molecular weight on graft copolymerization of dextran-methyl methacrylate. Polymer 21:819–824CrossRefGoogle Scholar
  9. 9.
    Onishi Y, Maruno S, Hokkoku S (1979) Graft copolymerization of methyl methacrylate onto dextran and some properties of copolymer. Kobunshi Ronbunshu 36:535–541CrossRefGoogle Scholar
  10. 10.
    Otsuka N et al (1972) The molecular-weight distribution of the grafted PMMA chains and molecular-weight of corresponding starch-fractions. Kobunshi Kagaku 29:930–935CrossRefGoogle Scholar
  11. 11.
    Brckway CE, Seaberg PA (1967) Grafting of polyacrylonitrile to granular corn starch. J Polym Sci A-1 Polym Chem 5:1313–1326CrossRefGoogle Scholar
  12. 12.
    Murata J, Ohya Y, Ouchi T (1966) Possibility of application of quaternary chitosan having pendant galactose residues as gene delivery tool. Carbohydr Polym 29:9–74Google Scholar
  13. 13.
    Sato T (2002) Carbohydrate polymer for gene delivery. Kobunshi 51:37–840CrossRefGoogle Scholar
  14. 14.
    McCutchan JH, Pagano JS (1968) Enhancement of the infectivity of simian virus 40 deoxyribonucleic acid with diethylaminoethyl-dextran. J Natl Cancer Inst 41:51–358Google Scholar
  15. 15.
    Warden D, Thorne HV (1969) Influence of diethylaminoethyl-dextran on uptake and degradation of polyoma virus deoxyribo-nucleic acid by mouse embryo cells. J Virol 4:380–387Google Scholar
  16. 16.
    Constantin T, Vendrely C (1969) Effect of DEAE-dextran on the incorporation of tritiated DNA by cultured rat cells. CR Soc Biol 163:300–305Google Scholar
  17. 17.
    Mack KD, Wei R, Elbagarri A, Abbey N, McGrath SD (1998) A novel method for DEAE-dextran mediated transfection of adherent primary cultured human macrophages. Immunol Methods 211:79–86CrossRefGoogle Scholar
  18. 18.
    Onisi Y, Kikuchi Y (2003) Study of the complex between DNA and DEAE-dextran. Kobunshi Ronbunshu 60:359–364CrossRefGoogle Scholar
  19. 19.
    Onisi Y, Kikuchi Y (2004) Study of the complex between RNA and DEAE-dextran. Kobunshi Ronbunshu 61:139–143CrossRefGoogle Scholar
  20. 20.
    Onishi Y (1987) US Patent 4816540Google Scholar
  21. 21.
    Onishi Y, Eshita Y, Murashita A, Mizuno M, Yoshida J (2005) Synthesis and characterization of 2-diethylaminoethyl (DEAE)-dextran-MMA graft copolymer for non-viral gene delivery vector. J Appl Polym Sci 98:9–14CrossRefGoogle Scholar
  22. 22.
    Higashihara J, Onishi Y, Mizuno M, Yoshida J, Tamori, N, Dieng H, Kato K, Okada T, Eshita Y (2005) Transfection of foreign genes into culture cells using novel DEAE-dextran copolymer as a non-viral gene carrier. In: The 55th annual meeting of southern region, the Japan Society of Medical Entomology and Zoology, Miyazaki Prefecture Japan, October 23, Abstract 15Google Scholar
  23. 23.
    Onishi Y, Eshita Y, Murashita A, Mizuno M, Yoshida J (2007) Characteristics of 2-diethylaminoethyl(DEAE)-dextran-MMA graft copolymer as a non-viral gene carrier. Nanomed Nanotech Biol Med 3:184–191CrossRefGoogle Scholar
  24. 24.
    Chinai S, Matlack JD, Resnic AL, Samuels RJ (1955) Polymethyl methacrylate: dilute solution properties by viscosity and light scattering. J Polym Sci 17:391–401CrossRefGoogle Scholar
  25. 25.
    Pottenger CR, Johnson DC (1970) Mechanism of cerium (IV) oxidation of glucose and cellulose. J Polym Sci 8:01–318CrossRefGoogle Scholar
  26. 26.
    Narita H, Okimoto S, Machida S (1969) Polymerization mechanism of methylmethacrylate initiated with ceric ion. Makromol Chem 125:5CrossRefGoogle Scholar
  27. 27.
    Namikawa R, Okazaki H, Nakanishi K, Matsuno R, Kamikubo T (1977) Diffusion of amino acids and saccharides in solutions of dextran and its derivatives. Agric Biol Chem 41:1003–1009CrossRefGoogle Scholar
  28. 28.
    Hintz HL, Johnson DC (1967) Mechanism of oxidation of cyclic alcohols by cerium (IV). J Org Chem 32:56–564CrossRefGoogle Scholar
  29. 29.
    Ardon M (1957) Oxidation of ethanol by ceric perchlorate. J Chem Soc 1957:1811–1815CrossRefGoogle Scholar
  30. 30.
    Duke FR, Forist AA (1949) The theory and kinetics of specific oxidation. III. The cerate–2,3-butanediol reaction in nitric acid solution. J Am Chem Soc 71:790–2792CrossRefGoogle Scholar
  31. 31.
    Duke FR, Bremer RF (1951) The theory and kinetics of specific oxidation. IV. The cerate 2,3-butanediol reactions in perchlorate solutions. J Am Chem Soc 73:179–5181Google Scholar
  32. 32.
    Morita H (1956) Characterization of starch and related polysaccharides by differential thermal analysis. Ann Chem 28:64–67CrossRefGoogle Scholar
  33. 33.
    Fox TG, Goode WE, Gratch S, Kincaid JF, Spell A, Stroupe JD (1958) Crystalline polymers of methyl methacrylate. J Am Chem Soc 80:1768–1769CrossRefGoogle Scholar
  34. 34.
    Elmer TH, Nordberg ME, Carrier GB, Korda FJ (1970) Phase separation in borosilicate glasses as seen by electron microscopy and scanning electron microscopy. J Am Ceram Soc 53(4):171–175CrossRefGoogle Scholar
  35. 35.
    Kargina OV, Adorova IV, Kabanov VA, Kargin VA (1960) Dokl Akad Nauk USSR 170:1130Google Scholar
  36. 36.
    Bamford CH, Shiki Z (1968) Free-radical template polymerization. Polymer 9:595–598CrossRefGoogle Scholar
  37. 37.
    Ferguson J, Shah SAO (1968) Further studies on polymerizations in interacting polymer systems. Eur Polym J 4:611–619CrossRefGoogle Scholar
  38. 38.
    Tsuchida E, Osada Y (1975) Effects of macromolecular matrix on the process of radical polymerization of ionizable monomers. J Polym Sci Polym Chem Ed 13:559–569CrossRefGoogle Scholar
  39. 39.
    Vogel MK, Cross RA, Bixler HJ (1970) Medical uses for polyelectrolyte complexes. J Macromol Sci-Chem A4(3):675–692Google Scholar
  40. 40.
    Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175(4023):720–731CrossRefGoogle Scholar
  41. 41.
    Sole A (1958) Die Stafoskopie der Tranen. Klin Monatsbl Augenheilkd 126:446–451Google Scholar
  42. 42.
    Nishioka K, Hara Y, Kamiya S, Matsuzawa Y, Iguchi M, Yamauchi A (1977) Crystals from vitreous. F Ophthal Jpn 28:579–586Google Scholar
  43. 43.
    Bloomfield VA (1997) DNA condensation by multivalent cations. Biopolymers 44:269–282CrossRefGoogle Scholar
  44. 44.
    Yoshikawa Y, Emi N, Kanbe T, Yoshikawa K, Saito H (1996) Folding and aggregation of DNA chains induced by complexation with lipospermine formation of a nucleosome-like structure and network assembly. FEBS Lett 396:71–76CrossRefGoogle Scholar
  45. 45.
    Karak N, Maliti S (1997) Dendritic polymers: a class of novel materials. J Polym Mater 14:107–122Google Scholar
  46. 46.
    Schreier JB (1969) Modification of deoxyribonuclease test medium for rapid identification of Serratia marcescens. Am J Clin Pathol 51:711–716Google Scholar
  47. 47.
    Maes R, Sedwick W, Vaheri A (1967) Interaction between DEAE-dextran and nucleic acids. Biochim Biophys Acta 134:269–76CrossRefGoogle Scholar
  48. 48.
    Pagano JS, McCutchan JH, Vaheri A (1967) Factors influencing the enhancement of the infectivity of poliovirus ribonucleic acid by diethylaminoethyl-dextran. J Virol 1:891–897Google Scholar
  49. 49.
    Price C, Woods DA (1973) Method for studying micellar aggregates in block and graft copolymers. Eur Polym Sci 9:827–830CrossRefGoogle Scholar
  50. 50.
    Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: Mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46(12 Pt 1):6387–6392Google Scholar
  51. 51.
    Allen TM, Chonn A (1987) Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett 223:42–46CrossRefGoogle Scholar
  52. 52.
    Oku N, Namba Y, Okada S (1992) Tumor accumulation of novel RES-avoiding liposomes. Biochim Biophys Acta 1126:255–260CrossRefGoogle Scholar
  53. 53.
    Savic R, Luo L, Eisenberg A, Maysinger D (2003) Micellar nanocontainers distribute to defined cytoplasmic organelles. Science 300:615–618CrossRefGoogle Scholar
  54. 54.
    Hamblin MR et al (2001) Polymer conjugate increases tumor targeting of photosensitizer. Cancer Res 61:7155–7162Google Scholar
  55. 55.
    Nishiyama N et al (2003) Free and N-(2-hydroxypropyl)methacrylamide copolymer-bound geldanamycin derivative induce different stress responses in A2780 human ovarian carcinoma cells. Cancer Res 63:7876–7882Google Scholar
  56. 56.
    Willstatter R, Pfannenstiel AI (1920) Über Succinyldiessigsäureester. Justus Liebigs Ann Chem 422:1–15CrossRefGoogle Scholar
  57. 57.
    Eshita Y et al (2009) Mechanism of introducing exogenous genes into cultured cells using DEAE-dextran-MMA graft copolymer as non-viral gene carrier. Molecules 14:2669–2683CrossRefGoogle Scholar
  58. 58.
    Onishi Y, Eshita Y, Mizuno M (2009) DEAE-dextran-MMA graft copolymer matrices for nonviral delivery of DNA. In: Jorgenson L, Nielson HM (eds) Delivery technologies for biopharmaceuticals. Wiley, West SussexGoogle Scholar
  59. 59.
    Onishi Y, Eshita Y, Murashita A, Mizuno M, Yoshida J (2008) A novel vector of 2-diethyl aminoethyl(DEAE)-dextran-MMA graft copolymer for non-viral gene delivery. J Gene Med 10:472Google Scholar
  60. 60.
    Onishi Y, Eshita Y, Mizuno M (2009) DEAE-dextran and DEAE-dextran-MMA graft copolymer for nonviral delivery of nucleic acids. In: Bartul Z, Trenor J (eds) Advances in nanotechnology, vol 3. Nova, New York, NYGoogle Scholar
  61. 61.
    Onishi Y, Eshita Y, Mizuno M (2010) DEAE-dextran and DEAE-dextran-MMA graft copolymer for nanomedicine. Polym ResJ 3:415–453Google Scholar
  62. 62.
    Eshita Y et al (2011) Mechanism of the introduction of exogenous genes into cultured cells using DEAE-Dextran-MMA graft copolymer as a non-viral gene carrier. II. Its thixotropy property. J Nanomed Nanotechnol 2:1–8Google Scholar
  63. 63.
    Yguerabide J, Yguerabide EE (1998) Light-scattering submicroscopic particles as highly fluorescent analogs and their use as tracer labels in clinical and biological applications. Anal Biochem 262:137–156CrossRefGoogle Scholar
  64. 64.
    NakanoT TK, YadeT OY (2001) Dibenzofulvene, a 1,1-diphenylethylene analogue, gives a π-stacked polymer by anionic, free-radical, and cationic catalysts. JACS 123(37):9182–9183CrossRefGoogle Scholar
  65. 65.
    Grants-in-Aid for Scientific Research on Innovative Areas, MEXT, Japan (Project No. 4201), Miyano S (2011) Cancer and supercomputer. CICSJ Bull 29:42–48Google Scholar
  66. 66.
    Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (KI) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099–3108CrossRefGoogle Scholar
  67. 67.
    Hill AV (1910) The possible effects of the aggregation of the molecules of hemoglobin on its dissociation curve. J Physiol 40(4):iv–vii, Retrieved 18 Mar 2009Google Scholar
  68. 68.
    Wadsworth P, Khodjakov A (2004) E pluribus unum: towards a universal mechanism for spindle assembly. Trends Cell Biol 14:413–419CrossRefGoogle Scholar
  69. 69.
    Minoura I, Muto E (2006) Dielectric measurement of individual microtubules using the electroorientation method. Biophys J 90:3739–3748CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Ryuju Science Co. LtdSetoJapan
  2. 2.Department of Infectious Diseases, Faculty of MedicineOita UniversityOitaJapan
  3. 3.The Center for Advanced Medicine and Clinical Research, Nagoya University HospitalShowa-ku, NagoyaJapan

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