Pharmaceutical and Medical Applications of Poly-Gamma-Glutamic Acid

Chapter
Part of the Microbiology Monographs book series (MICROMONO, volume 15)

Abstract

Poly(amino acid)s have received considerable attention for biomedical applications. Poly(γ-glutamic acid) (γ-PGA), a natural polymer, is synthesized by several gram-positive bacteria. γ-PGA is anionic, water soluble, biodegradable, edible, nontoxic, and nonimmunogenic for humans and the environment, and its α-carboxylate side chains can be chemically modified to introduce various drugs, or to modulate the amphiphilicity of the polymer. These features of γ-PGA are very useful for pharmaceutical and biomedical applications. This paper reviews the preparation of polymeric drugs, nanoparticles, and hydrogels composed of γ-PGA and their medical applications as drug carriers and tissue-engineering materials. γ-PGA–drug conjugates, nanoparticles, and hydrogels fabricated from γ-PGA or its derivatives have wide application for drug delivery system and regenerative medical technique.

References

  1. Akagi T, Higashi M, Kaneko T, Kida T, Akashi M (2005a) In vitro enzymatic degradation of nanoparticles prepared from hydrophobically-modified poly(γ-glutamic acid). Macromol Biosci 5:598–602PubMedGoogle Scholar
  2. Akagi T, Kaneko T, Kida T, Akashi M (2005b) Preparation and characterization of biodegradable nanoparticles based on poly(γ-glutamic acid) with L-phenylalanine as a protein carrier. J Control Release 108:226–236PubMedGoogle Scholar
  3. Akagi T, Higashi M, Kaneko T, Kida T, Akashi M (2006a) Hydrolytic and enzymatic degradation of nanoparticles based on amphiphilic poly(γ-glutamic acid)-graft-L-phenylalanine copolymer. Biomacromolecules 7:297–303PubMedGoogle Scholar
  4. Akagi T, Kaneko T, Kida T, Akashi M (2006b) Multifunctional conjugation of proteins on/into core-shell type nanoparticles prepared by amphiphilic poly(γ-glutamic acid). J Biomater Sci Polym Ed 17:875–892PubMedGoogle Scholar
  5. Akagi T, Baba M, Akashi M (2007a) Preparation of nanoparticles by the self-organization of polymers consisting of hydrophobic and hydrophilic segments: potential applications. Polymer 48:6729–6747Google Scholar
  6. Akagi T, Wang X, Uto T, Baba M, Akashi M (2007b) Protein direct delivery to dendritic cells using nanoparticles based on amphiphilic poly(amino acid) derivatives. Biomaterials 28:3427–3436PubMedGoogle Scholar
  7. Akiyoshi K, Ueminami A, Kurumada S, Nomura Y (2000) Self-association of cholesteryl-bearing poly(L-lysine) in water and control of its secondary structure by host−guest interaction with cyclodextrin. Macromolecules 33:6752–6756Google Scholar
  8. Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303:1818–1822PubMedGoogle Scholar
  9. Arimura H, Ohya Y, Ouchi T (2005) Formation of core-shell type biodegradable polymeric micelles from amphiphilic poly(aspartic acid)-block-polylactide diblock copolymer. Biomacromolecules 6:720–725PubMedGoogle Scholar
  10. Asano T, Anai M, Sakoda H, Fujishiro M, Ono H, Kurihara H, Uchijima Y (2004) SGLT as a therapeutic target. Drugs Future 29:461–466Google Scholar
  11. Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252PubMedGoogle Scholar
  12. Bodnar M, Kjoniksen AL, Molnar RM, Hartmann JF, Daroczi L, Nystrom B, Borbely J (2008) Nanoparticles formed by complexation of poly-γ-glutamic acid with lead ions. J Hazard Mater 153:1185–1192PubMedGoogle Scholar
  13. Cohen S, Yoshioka T, Lucarelli M, Hwang LH, Langer R (1991) Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres. Pharm Res 8:713–720PubMedGoogle Scholar
  14. Damg C, Michel C, Aprahamian M, Couvreur P, Devissagnet JP (1990) Nanocapsules as carriers for oral peptide delivery. J Cantrol Release 13:233–239Google Scholar
  15. Deuber HJ, Schultz W (1991) Reduced lipid concentration during four years of dialysis with low molecular weight heparin. Kidney Int 40:496–500PubMedGoogle Scholar
  16. Di Paolo A, Danesi R, Falcone A, Cionini L, Vannozzi F, Masi G, Allegrini G, Mini E, Bocci G, Conte PF, Del Tacca M (2001) Relationship between 5-fluorouracil disposition, toxicity and dihydropyrimidine dehydrogenase activity in cancer patients. Ann Oncol 12:1301–1306PubMedGoogle Scholar
  17. Dou H, Jiang M, Peng H, Chen D, Hong Y (2003) pH-dependent self-assembly: micellization and micelle-hollow-sphere transition of cellulose-based copolymers. Angew Chem Int Ed 42:1516–1519Google Scholar
  18. Edlund U, Albertsson AC (2000) Degradable polymer microspheres for controlled drug delivery. Adv Polym Sci 157:67–112Google Scholar
  19. Elamanchili P, Diwan M, Cao M, Samuel J (2004) Characterization of poly(D, L-lactic-co-glycolic acid) based nanoparticulate system for enhanced delivery of antigens to dendritic cells. Vaccine 22:2406–2412PubMedGoogle Scholar
  20. Fahama S, Hileman RE, Fromm JR, Linhardt RJ, Rees DC (1996) Heparin structure and interactions with basic fibroblast growth factor. Science 271:1116–1120Google Scholar
  21. Fallon RJ, Schwartz AL (1989) Receptor-mediated delivery of drugs to hepatocytes. Adv Drug Deliv Rev 4:49–63Google Scholar
  22. Gamvrellis A, Leong D, Hanley JC, Xiang SD, Mottram P, Plebanski M (2004) Vaccines that facilitate antigen entry into dendritic cells. Immunol Cell Biol 82:506–516PubMedGoogle Scholar
  23. Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC (2005) Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release 109:169–188PubMedGoogle Scholar
  24. Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R (1994) Biodegradable long-circulating polymeric nanospheres. Science 263:1600–1603PubMedGoogle Scholar
  25. Hajdu I, Bodnar M, Filipcsei G, Hartmann JF, Daroczi L, Zrinyi M, Borbely J (2009) Nanoparticles prepared by self-assembly of chitosan and poly-γ-glutamic acid. Colloid Polym Sci 286:343–350Google Scholar
  26. Hans ML, Lowman AM (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327Google Scholar
  27. Harding CV, Song R (1994) Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J Immunol 153:4925–4933PubMedGoogle Scholar
  28. Hartig SM, Greene RR, DasGupta J, Carlesso G, Dikov MM, Prokop A, Davidson JM (2007) Multifunctional nanoparticulate polyelectrolyte complexes. Pharm Res 24:2353–2369PubMedGoogle Scholar
  29. Holowka EP, Pochan DJ, Deming TJ (2005) Charged polypeptide vesicles with controllable diameter. J Am Chem Soc 127:12423–12428PubMedGoogle Scholar
  30. Holowka EP, Sun VZ, Kamei DT, Deming TJ (2007) Polyarginine segments in block copolypeptides drive both vesicular assembly and intracellular delivery. Nat Mater 6:52–57PubMedGoogle Scholar
  31. Hsieh CY, Tsai SP, Wang DM, Chang YN, Hsieh HJ (2005) Preparation of γ-PGA/chitosan composite tissue engineering matrices. Biomaterials 26:5617–5623PubMedGoogle Scholar
  32. Hubbell JA (2003) Materials as morphogenetic guides in tissue engineering. Curr Opin Biotechnol 14:551–558PubMedGoogle Scholar
  33. Ikumi Y, Kida T, Sakuma S, Yamashita S, Akashi M (2008) Polymer-phloridzin conjugates as an anti-diabetic drug that inhibits glucose absorption through the Na+/glucose cotransporter (SGLT1) in the small intestine. J Control Release 125:42–49PubMedGoogle Scholar
  34. Jaturanpinyo M, Harada A, Yuan X, Kataoka K (2004) Preparation of bionanoreactor based on core-shell structured polyion complex micelles entrapping trypsin in the core cross-linked with glutaraldehyde. Bioconjugate Chem 15:344–348Google Scholar
  35. Jelinkova M, Strohalm J, Plocova D, Subr V, Stcastny M, Ulbrich K, Rihova B (1998) Targeting of human and mouse T-lymphoctes by monoclonal antibody-HPMA copolymer-doxorubicin conjugates directed against different T-cell surface antigens. J Control Release 52:253–270PubMedGoogle Scholar
  36. Jeong JH, Kang HS, Yang SR, Kim JD (2003) Polymer micelle-like aggregates of novel amphiphilic biodegradable poly(asparagine) grafted with poly(caprolactone). Polymer 44:583–591Google Scholar
  37. Jilek S, Merkle HP, Walter E (2007) DNA-loaded biodegradable microparticles as vaccine delivery systems and their interaction with dendritic cells. Adv Drug Deliv Rev 57:377–390Google Scholar
  38. Jin Y, Li J, Rong LF, Lu XW, Huang Y, Xu SY (2005) Pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated by galactosylceramide liposomes in mice. Acta Pharmacol Sin 26:250–256PubMedGoogle Scholar
  39. Joyce J, Cook J, Chabot D, Hepler R, Shoop W, Xu Q, Stambaugh T, Aste-Amezaga M, Wang S, Indrawati L, Bruner M, Friedlander A, Keller P, Caulfield M (2006) Immunogenicity and protective efficacy of Bacillus anthracis poly-γ-D-glutamic acid capsule covalently coupled to a protein carrier using a novel triazine-based conjugation strategy. J Biol Chem 281:4831–4843PubMedGoogle Scholar
  40. Kakizawa Y, Kataoka K (2002) Block copolymer micelles for delivery of gene and related compounds. Adv Drug Deliv Rev 54:203–222PubMedGoogle Scholar
  41. Kaneko T, Higashi M, Matsusaki M, Akagi T, Akashi M (2005) Self-assembled soft nanofibrils of amphipathic polypeptides and their morphological transformation. Chem Mater 17:2484–2486Google Scholar
  42. Kang N, Perron ME, Prudhomme RE, Zhang Y, Gaucher G, Leroux JC (2005) Stereocomplex block copolymer micelles: core-shell nanostructures with enhanced stability. Nano Lett 5:315–319PubMedGoogle Scholar
  43. Kang HS, Park SH, Lee YG, Son I (2007) Polyelectrolyte complex hydrogel composed of chitosan and poly(γ-glutamic acid) for biological application: preparation, physical properties, and cytocompatibility. J Appl Polym Sci 103:386–394Google Scholar
  44. Kataoka K, Matsumoto T, Yokoyama M, Okano T, Sakurai Y, Fukushima S, Okamoto K, Kwon GS (2000) Doxorubicin-loaded poly(ethylene glycol)-poly(β-benzyl-L-aspartate) copolymer micelles: their pharmaceutical characteristics and biological significance. J Control Release 64:143–153PubMedGoogle Scholar
  45. Keller KM, Brauer PR, Keller JM (1989) Modulation of cell surface heparan sulfate structure by growth of cells in the presence of chlorate. Biochemistry 28:8100–8107PubMedGoogle Scholar
  46. Kelton JC (1986) Heparin-induced thrombocyopenia. Haemostasis 16:173–186PubMedGoogle Scholar
  47. Kim TW, Lee TY, Bae HC, Hahm JH, Kim YH, Park C, Kang TH, Kim CJ, Sung MH, Poo H (2007) Oral administration of high molecular mass poly-γ-glutamate induces NK cell-mediated antitumor immunity. J Immunol 179:775–780PubMedGoogle Scholar
  48. Kim H, Akagi T, Akashi M (2009) Preparation of size tunable amphiphilic poly(amino acid) nanoparticles. Macromol Biosci 9:842–848PubMedGoogle Scholar
  49. King EC, Watkins WJ, Blacker AJ, Bugg TDH (1998) Covalent modification in aqueous solution of poly-γ-D-glutamic acid from Bacillus licheniformis. J Polym Sci A Polym Chem 36:1995–1999Google Scholar
  50. Kishida A, Goto H, Murakami K, Kakinoki K, Endo T, Akashi M (1998a) Polymer drugs and polymeric drugs IX: Synthesis and 5-fluorouracil release profiles of biodegradable polymeric prodrugs γ-poly(α-hydroxymethyl-5-fluorouracil-glutamate). J Bioact Compat Polym 13:222–233Google Scholar
  51. Kishida A, Murakami K, Goto H, Kubota H, Endo T, Akashi M (1998b) Polymer drugs and polymeric drugs X: Slow release of 5-fluorouracil from biodegradable poly(γ-glutamic acid) and its benzyl ester matrixes. J Bioact Compat Polym 13:270–278Google Scholar
  52. Kubler-Kielb J, Liu TY, Mocca C, Majadly F, Robbins JB, Schneerson R (2006) Additional conjugation methods and immunogenicity of Bacillus anthracis poly-γ-D-glutamic acid-protein conjugates. Infect Immun 74:4744–4749PubMedGoogle Scholar
  53. Kubota H, Matsunobu T, Uotani K, Takebe H, Satoh A, Tanaka T, Taniguchi M (1993) Production of poly(γ-glutamic acid) by Bacillus subtilis F-2-01. Biosci Biotech Biochem 57:1212–1213Google Scholar
  54. Kunath K, Kopeckova P, Minko T, Kopecek J (2000) HPMA copolymer-anticancer drug-OV-TL16 antibody conjugates. 3. The effect of free and polymer-bound adriamycin on the expression of some genes in the OVCAR-3 human ovarian carcinoma cell line. Eur J Pharm Biopharm 49:11–15PubMedGoogle Scholar
  55. Kurosaki T, Kitahara T, Fumoto S, Nishida K, Nakamura J, Niidome T, Kodama Y, Nakagawa H, To H, Sasaki H (2009) Ternary complexes of pDNA, polyethylenimine, and γ-polyglutamic acid for gene delivery systems. Biomaterials 30:2846–2853PubMedGoogle Scholar
  56. Laner R, Vacanti JP (1993) Tissue engineering. Science 260:920–926Google Scholar
  57. Lee KY, Mooney DJ (2001) Hydrogel for tissue engineering. Chem Rev 101:1869–1879PubMedGoogle Scholar
  58. Lee ES, Shin HJ, Na K, Bae YH (2003) Poly(L-histidine)-PEG block copolymer micelles and pH-induced destabilization. J Control Release 90:363–374PubMedGoogle Scholar
  59. Lee J, Cho EC, Cho K (2004) Incorporation and release behavior of hydrophobic drug in functionalized poly(D, L-lactide)-block-poly(ethylene oxide) micelles. J Control Release 94:323–335PubMedGoogle Scholar
  60. Lee PW, Peng SF, Su CJ, Mi FL, Chen HL, Wei MC, Lin HJ, Sung HW (2008) The use of biodegradable polymeric nanoparticles in combination with a low-pressure gene gun for transdermal DNA delivery. Biomaterials 29:742–751PubMedGoogle Scholar
  61. Lee TY, Kim YH, Yoon SW, Choi JC, Yang JM, Kim CJ, Schiller JT, Sung MH, Poo HR (2009) Oral administration of poly-γ-glutamate induces TLR4- and dendritic cell-dependent antitumor effect. Cancer Immunol Immunother 58:1781–1794PubMedGoogle Scholar
  62. Leonard CD, Scribner BH (1969) Subdural hematoma in patients undergoing hemodialysis. Lancet 2:239–249PubMedGoogle Scholar
  63. Letchford K, Burt H (2007) A review of the formation and classification of amphiphilic block copolymer nanoparticulate structures: micelles, nanospheres, nanocapsules and polymersomes. Eur J Pharm Biopharm 65:259–269PubMedGoogle Scholar
  64. Li C (2002) Poly(L-glutamic acid)–anticancer drug conjugates. Adv Drug Deliv Rev 54:695–713PubMedGoogle Scholar
  65. Li SD, Huang L (2006) Gene therapy progress and prospects: non-viral gene therapy by systemic delivery. Gene Ther 13:1313–1319PubMedGoogle Scholar
  66. Li C, Wallace S (2008) Polymer-drug conjugates: recent development in clinical oncology. Adv Drug Delivery Rev 60:886–898Google Scholar
  67. Li C, Yu DF, Newman RA, Cabral F, Stephens LC, Hunter N, Milas L, Wallace S (1998) Complete regression of well-established tumors using a novel water-soluble poly(L-glutamic acid)-paclitaxel conjugate. Cancer Res 58:2404–2409PubMedGoogle Scholar
  68. Li C, Newman RA, Wu QP, Ke S, Chen W, Hutto T, Kan Z, Brannan MD, Charnsangavej C, Wallace S (2000) Biodistribution of paclitaxel and poly(L-glutamic acid)-paclitaxel conjugate in mice with ovarian OCa-1 tumor. Cancer Chemother Pharmacol 46:416–422PubMedGoogle Scholar
  69. Liang HF, Yang TF, Huang CT, Chen MC, Sung HW (2005) Preparation of nanoparticles composed of poly(γ-glutamic acid)-poly(lactide) block copolymers and evaluation of their uptake by HepG2 cells. J Control Release 105:213–225PubMedGoogle Scholar
  70. Liang HF, Chen SC, Chen MC, Lee PW, Chen CT, Sung HW (2006a) Paclitaxel-loaded poly(γ-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system against cultured HepG2 cells. Bioconjugate Chem 17:291–299Google Scholar
  71. Liang HF, Chen CT, Chen SC, Kulkarni AR, Chiu YL, Chen MC, Sung HW (2006b) Paclitaxel-loaded poly(γ-glutamic acid)-poly(lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials 27:2051–2059PubMedGoogle Scholar
  72. Lin YH, Chung CK, Chen CT, Liang HF, Chen SC, Sung HW (2005) Preparation of nanoparticles composed of chitosan/poly-γ-glutamic acid and evaluation of their permeability through Caco-2 cells. Biomacromolecules 6:1104–1112PubMedGoogle Scholar
  73. Lin J, Zhang S, Chen T, Lin S, Jin H (2007a) Micelle formation and drug release behavior of polypeptide graft copolymer and its mixture with polypeptide block copolymer. Int J Pharm 336:49–57PubMedGoogle Scholar
  74. Lin YH, Mi FL, Chen CT, Chang WC, Peng SF, Liang HF, Sung HW (2007b) Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery. Biomacromolecules 8:146–152PubMedGoogle Scholar
  75. Lin YH, Sonaje K, Lin KM, Juang JH, Mi FL, Yang HW, Sung HW (2008) Multi-ion-crosslinked nanoparticles with pH-responsive characteristics for oral delivery of protein drugs. J Control Release 132:141–149PubMedGoogle Scholar
  76. Maeda H (2001) SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy. Adv Drug Delivery Rev 46:169–185Google Scholar
  77. Maeda H, Sawa T, Konno T (2001) Mechanism of tumor-targeted delivery of macromolecular drugs, including the EPR effect in solid tumor and clinical overview of the prototype polymeric drug SMANCS. J Control Release 74:47–61PubMedGoogle Scholar
  78. Mann A, Richa R, Ganguli M (2008) DNA condensation by poly-L-lysine at the single molecule level: role of DNA concentration and polymer length. J Control Release 125:252–262PubMedGoogle Scholar
  79. Matsuo K, Yoshikawa T, Oda A, Akagi T, Akashi M, Okada N, Nakagawa S (2007) Efficient generation of antigen-specific cellular immunity by vaccination with poly(γ-glutamic acid) nanoparticles entrapping endoplasmic reticulum-targeted peptides. Biochem Biophys Res Commun 362:1069–1072PubMedGoogle Scholar
  80. Matsusaki M, Akashi M (2005) Novel functional biodegradable polymer IV: pH-sensitive controlled release of fibroblast growth factor-2 from a poly(γ-glutamic acid)sulfonate matrix for tissue engineering. Biomacromolecules 6:3351–3356PubMedGoogle Scholar
  81. Matsusaki M, Serizawa T, Kishida A, Endo T, Akashi M (2002) Novel functional biodegradable polymer: Synthesis and anticoagulant activity of poly(γ-glutamic acid)sulfonate (γ-PGA-sulfonate). Bioconjugate Chem 13:23–28Google Scholar
  82. Matsusaki M, Hiwatari K, Higashi M, Kaneko T, Akashi M (2004) Stably-dispersed and surface-functional bionanoparticles prepared by self-assembling amphipathic polymers of hydrophilic poly(γ-glutamic acid) bearing hydrophobic amino acids. Chem Lett 33:398–399Google Scholar
  83. Matsusaki M, Serizawa T, Kishida A, Akashi M (2005a) Novel functional biodegradable polymer II: Fibroblast growth factor-2 activities of poly(γ-glutamic acid)sulfonate. Biomacromolecules 6:400–407PubMedGoogle Scholar
  84. Matsusaki M, Serizawa T, Kishida A, Akashi M (2005b) Novel functional biodegradable polymer III: The construction of poly(γ-glutamic acid)sulfonate hydrogel with fibroblast growth factor-2 activity. J Biomed Mater Res 73A:485–491Google Scholar
  85. Matsusaki M, Yoshida H, Akashi M (2007) The construction of 3D-engineered tissues composed of cells and extracellular matrices by hydrogel template approach. Biomaterials 28:2729–2737PubMedGoogle Scholar
  86. Mauzac M, Jozefonvictz J (1984) Anticoagulant activitiy of dextran derivatives. Part I: Synthesis and characterization. Biomaterials 5:301–304PubMedGoogle Scholar
  87. Mi FL, Wu YY, Lin YH, Sonaje K, Ho YC, Chen CT, Juang JH, Sung HW (2008) Oral delivery of peptide drugs using nanoparticles self-assembled by poly(γ-glutamic acid) and a chitosan derivative functionalized by trimethylation. Bioconjugate Chem 19:1248–1255Google Scholar
  88. Minko T, Kopeckova P, Kopecek J (2000) Efficacy of the chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma. Int J Cancer 86:108–117PubMedGoogle Scholar
  89. Morillo M, Martinez de Ilarduya A, Munoz-Guerra S (2001) Comblike alkyl esters of biosynthetic poly(γ-glutamic acid). 1. Synthesis and characterization. Macromolecules 34:7868–7875Google Scholar
  90. Muller M, Reihs T, Ouyang W (2005) Needlelike and spherical polyelectrolyte complex nanoparticles of poly(L-lysine) and copolymers of maleic acid. Langmuir 21:465–469PubMedGoogle Scholar
  91. Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM (2008) Nano/micro technologies for delivering macromolecular therapeutics using poly(D, L-lactide-co-glycolide) and its derivatives. J Control Release 125:193–209PubMedGoogle Scholar
  92. Muzzarelli RAA, Tanfani F, Emanuelli M (1984) Sulfated N-(carboxymethyl)chitosans: Novel blood anticoagulants. Carbohydr Res 126:225–231PubMedGoogle Scholar
  93. Na K, Lee KH, Bae YH (2004) pH-sensitivity and pH-dependent interior structural change of self-assembled hydrogel nanoparticles of pullulan acetate/oligo-sulfonamide conjugate. J Control Release 97:513–525PubMedGoogle Scholar
  94. Nam YS, Kang HS, Park JY, Park TG, Han SH, Chang IS (2003) New micelle-like polymer aggregates made from PEI-PLGA diblock copolymers: micellar characteristics and cellular uptake. Biomaterials 24:2053–2059PubMedGoogle Scholar
  95. Nishimura S, Tokura S (1987) Preparation and antithrombogenic activities of heparinoid from 6-O-(carboxymethyl)chitin. Int J Biol Macromol 9:225–232Google Scholar
  96. Nixon DF, Hioe C, Chen PD, Bian Z, Kuebler P, Li ML, Qiu H, Li XM, Singh M, Richardson J, McGee P, Zamb T, Koff W, Wang CY, O'Hagan D (1996) Synthetic peptides entrapped in microparticles can elicit cytotoxic T cell activity. Vaccine 14:1523–1530PubMedGoogle Scholar
  97. Obst M, Steinbuchel A (2004) Microbial degradation of poly(amino acid)s. Biomacromolecules 5:1166–1176PubMedGoogle Scholar
  98. Okamoto S, Yoshii H, Akagi T, Akashi M, Ishikawa T, Okuno Y, Takahashi M, Yamanishi K, Mori Y (2007) Influenza hemagglutinin vaccine with poly(γ-glutamic acid) nanoparticles enhances the protection against influenza virus infection through both humoral and cell-mediated immunity. Vaccine 25:8270–8278PubMedGoogle Scholar
  99. Okamoto S, Yoshii H, Ishikawa T, Akagi T, Akashi M, Takahashi M, Yamanishi K, Mori Y (2008) Single dose of inactivated Japanese encephalitis vaccine with poly(γ-glutamic acid) nanoparticles provides effective protection from Japanese encephalitis virus. Vaccine 26:589–594PubMedGoogle Scholar
  100. Okamoto S, Matsuura M, Akagi T, Akashi M, Tanimoto T, Ishikawa T, Takahashi M, Yamanishi K, Mori Y (2009) Poly(γ-glutamic acid) nano-particles combined with mucosal influenza virus hemagglutinin vaccine protects against influenza virus infection in mice. Vaccine 27:5896–5905PubMedGoogle Scholar
  101. Oppermann FB, Fickaitz S, Steinbiichel A (1998) Biodegradation of polyamides. Polym Degrad Stab 59:337–344Google Scholar
  102. Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347PubMedGoogle Scholar
  103. Panyam J, Dali MM, Sahoo SK, Ma W, Chakravarthi SS, Amidon GL, Levy RJ, Labhasetwar V (2003) Polymer degradation and in vitro release of a model protein from poly(D, L-lactide-co-glycolide) nano- and microparticles. J Control Release 92:173–187PubMedGoogle Scholar
  104. Peng SF, Yang MJ, Su CJ, Chen HL, Lee PW, Wei MC, Sung HW (2009) Effects of incorporation of poly(γ-glutamic acid) in chitosan/DNA complex nanoparticles on cellular uptake and transfection efficiency. Biomaterials 30:1797–1808PubMedGoogle Scholar
  105. Pinzani V, Bressolle F, Haug IJ, Galtier M, Blayac JP, Balmes P (1994) Cisplatin-induced renal toxicity and toxicity-modulating strategies: a review. Cancer Chemother Pharmacol 35:1–9PubMedGoogle Scholar
  106. Portilla-Arias JA, Camargo B, Garcia-Alvarez M, Martinez de Ilarduya A, Munoz-Guerra S (2009) Nanoparticles made of microbial poly(γ-glutamate)s for encapsulation and delivery of drugs and proteins. J Biomater Sci Polym Ed 20:1065–1079PubMedGoogle Scholar
  107. Prodhomme EJ, Tutt AL, Glennie MJ, Bugg TD (2003) Multivalent conjugates of poly-γ-D-glutamic acid from Bacillus licheniformis with antibody F(ab′) and glycopeptide ligands. Bioconjugate Chem 14:1148–1155Google Scholar
  108. Quellec P, Gref R, Perrin L, Dellacherie E, Sommer F, Verbavatz JM, Alonso MJ (1998) Protein encapsulation within polyethylene glycol-coated nanospheres. I. Physicochemical characterization. J Biomed Mater Res 42:45–54PubMedGoogle Scholar
  109. Radu JEF, Novak L, Hartmann JF, Beheshti N, Kjoniksen AL, Nystrom B, Borbely J (2008) Structural and dynamical characterization of poly-γ-glutamic acid-based cross-linked nanoparticles. Colloid Polym Sci 286:365–376Google Scholar
  110. Reihs T, Muller M, Lunkwitz K (2004) Preparation and adsorption of refined polyelectrolyte complex nanoparticles. J Colloid Interface Sci 271:69–79PubMedGoogle Scholar
  111. Rhie GE, Roehrl MH, Mourez M, Collier RJ, Mekalanos JJ, Wang JY (2003) A dually active anthrax vaccine that confers protection against both bacilli and toxins. Proc Natl Acad Sci USA 100:10925–10930PubMedGoogle Scholar
  112. Ringsdorf H (1975) Structure and properties of pharmacologically active polymers. J Polym Sci Symp 51:135–153Google Scholar
  113. Sah H (1999) Stabilization of proteins against methylene chloride / water interface induced denaturation and aggregation. J Control Release 58:143–151PubMedGoogle Scholar
  114. Sakuma S, Suzuki N, Kikuchi H, Hiwatari K, Arikawa K, Kishida A, Akashi M (1997) Oral peptide delivery using nanoparticles composed of novel graft copolymers having hydrophobic backbone and hydrophilic branches. Int J Pharm 149:93–106Google Scholar
  115. Sakuma S, Hayashi M, Akashi M (2001) Design of nanoparticles composed of graft copolymers for oral peptide delivery. Adv Drug Deliv Rev 47:21–37PubMedGoogle Scholar
  116. Sakuma S, Sagawa T, Masaoka Y, Kataoka M, Yamashita S, Shirasaka Y, Tamai I, Ikumi Y, Kida T, Akashi M (2009) Stabilization of enzyme-susceptible glucoside bonds of phloridzin through conjugation with poly(γ-glutamic acid). J Control Release 133:125–131PubMedGoogle Scholar
  117. Sanda F, Fujiyama T, Endo T (2001) Chemical synthesis of poly-γ-glutamic acid by polycondensation of γ-glutamic acid dimer: synthesis and reaction of poly-γ-glutamic acid methyl ester. J Polym Sci A Polym Chem 39:732–741Google Scholar
  118. Sanda F, Fujiyama T, Endo T (2002) Stepwise synthesis of γ-glutamic acid 16-mer. Macromol Chem Phys 203:727–734Google Scholar
  119. Satchi-Fainaro R, Duncan R, Barnes CM (2000) Polymer therapeutics for cancer: current status and future challenges. Adv Polym Sci 193:1–65Google Scholar
  120. Schneerson R, Kubler-Kielb J, Liu TY, Dai ZD, Leppla SH, Yergey A, Backlund P, Shiloach J, Majadly F, Robbins JB (2003) Poly(γ-D-glutamic acid) protein conjugates induce IgG antibodies in mice to the capsule of Bacillus anthracis: a potential addition to the anthrax vaccine. Proc Natl Acad Sci USA 100:8945–8950PubMedGoogle Scholar
  121. Shih IL, Van YT (2001) The production of poly(γ-glutamic acid) from microorganisms and its various application. Bioresource Technol 79:207–225Google Scholar
  122. Shimokuri T, Kaneko T, Serizawa T, Akashi M (2004) Preparation and thermosensitivity of naturally occurring polypeptide poly(γ-glutamic acid) derivatives modified by alkyl groups. Macromol Biosci 4:407–411PubMedGoogle Scholar
  123. Sonaje K, Lin YH, Juang JH, Wey SP, Chen CT, Sung HW (2009) In vivo evaluation of safety and efficacy of self-assembled nanoparticles for oral insulin delivery. Biomaterials 30:2329–2339PubMedGoogle Scholar
  124. Sutherland MD, Kozel TR (2009) Macrophage uptake, intracellular localization, and degradation of poly-γ-D-glutamic acid, the capsular antigen of Bacillus anthracis. Infect Immun 77:532–538PubMedGoogle Scholar
  125. Sutherland MD, Thorkildson P, Parks SD, Kozel TR (2008) In vivo fate and distribution of poly-γ-D-glutamic acid, the capsular antigen from bacillus anthracis. Infect Immun 76:899–906PubMedGoogle Scholar
  126. Suzuki K, Yumura T, Tanaka Y, Serizawa T, Akashi M (2000) Interpenetrating inorganic-organic hybrid gels: Preparation of hybrid and replica gels. Chem Lett 29:1380–1381Google Scholar
  127. Tachibana Y, Kurisawa M, Uyama H, Kobayashi S (2003) Thermo- and pH-responsive biodegradable poly(α-N-substituted γ-glutamine)s. Biomacromolecules 4:1132–1134PubMedGoogle Scholar
  128. Torchilin VP (2006) Multifunctional nanocarriers. Adv Drug Delivery Rev 58:1532–1555Google Scholar
  129. Tsujihara K, Hongu M, Saito K, Inamasu M, Arakawa K, Oku A, Matsumoto M (1996) Na+-glucose cotransporter inhibitors as antidiabetics. I. synthesis and pharmacological properties of 4’-dehydroxyphlorizin derivatives based on a new concept. Chem Pharm Bull 44:1174–1180PubMedGoogle Scholar
  130. Uto T, Wang X, Sato K, Haraguchi M, Akagi T, Akashi M, Baba M (2007) Targeting of antigen to dendritic cells with poly(γ-glutamic acid) nanoparticles induce antigen-specific humoral and cellular immunity. J Immunol 178:2979–2986PubMedGoogle Scholar
  131. Uto T, Akagi T, Hamasaki T, Akashi M, Baba M (2009a) Modulation of innate and adaptive immunity by biodegradable nanoparticles. Immunol Lett 125:46–52PubMedGoogle Scholar
  132. Uto T, Wang X, Akagi T, Zenkyu R, Akashi M, Baba M (2009b) Improvement of adaptive immunity by antigen-carrying biodegradable nanoparticles. Biochem Biophys Res Commun 379:600–604PubMedGoogle Scholar
  133. Vasir JK, Labhasetwar V (2007) Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Delivry Rev 59:718–728Google Scholar
  134. Wang TT, Fellows PF, Leighton TJ, Lucas AH (2004) Induction of opsonic antibodies to the γ-D-glutamic acid capsule of Bacillus anthracis by immunization with a synthetic peptide-carrier protein conjugate. FEMS Immunol Med Microbiol 40:231–237PubMedGoogle Scholar
  135. Wang X, Akagi T, Akashi M, Baba M (2007a) Development of core-corona type polymeric nanoparticles as an anti-HIV-1 vaccine. Mini-Rev Org Chem 4:281–290Google Scholar
  136. Wang X, Uto T, Akagi T, Akashi M, Baba M (2007b) Induction of potent CD8+ T-cell responses by novel biodegradable nanoparticles carrying human immunodeficiency virus type 1 gp120. J Virol 81:10009–10016PubMedGoogle Scholar
  137. Wang X, Uto T, Akagi T, Akashi M, Baba M (2008) Poly(γ-glutamic Acid) nanoparticles as an efficient antigen delivery and adjuvant system: potential for an anti-AIDS vaccine. J Med Virol 80:11–19PubMedGoogle Scholar
  138. Weber J (1990) Poly(γ-glutamic acid)s are the major constituents of nematocysts in Hydra (Hydrozoa, Cnidaria). J Biol Chem 265:9664–9669PubMedGoogle Scholar
  139. Ye H, Jin L, Hu R, Yi Z, Li J, Wu Y, Xi X, Wu Z (2006) Poly(γ, L-glutamic acid)-cisplatin conjugate effectively inhibits human breast tumor xenografted in nude mice. Biomaterials 27:5958–5965PubMedGoogle Scholar
  140. Yoshida H, Klinkhammer K, Matsusaki M, Moller M, Klee D, Akashi M (2009a) Disulfide-crosslinked electrospun poly(γ-glutamic acid) nonwovens as reduction-responsive scaffolds. Macromol Biosci 9:568–574PubMedGoogle Scholar
  141. Yoshida H, Matsusaki M, Akashi M (2009b) Scaffold-mediated 2D cellular orientations for construction of three dimensionally engineered tissues composed of oriented cells and extracellular matrices. Adv Funct Mater 19:1001–1007Google Scholar
  142. Yoshida H, Matsusaki M, Akashi M (2010) Development of thick and highly cell-incorporated engineered tissues by hydrogel template approach with basic fibroblast growth factor or ascorbic acid. J Biomater Sci Polymer Ed 21:415–428Google Scholar
  143. Yoshikawa T, Okada N, Oda A, Matsuo K, Matsuo MY, Yoshioka Y, Akagi T, Akashi M, Nakagawa S (2008a) Development of amphiphilic γ-PGA-nanoparticle based tumor vaccine: Potential of the nanoparticulate cytosolic protein delivery carrier. Biochem Biophys Res Commun 366:408–413PubMedGoogle Scholar
  144. Yoshikawa T, Okada N, Oda A, Matsuo K, Matsuo K, Kayamuro H, Ishii Y, Yoshinaga T, Akagi T, Akashi M, Nakagawa S (2008b) Nanoparticles built by self-assembly of am phiphilic poly(γ-glutamic acid) can deliver antigens to antigen-presenting cells with high efficiency: A new tumor-vaccine carrier for eliciting effector T cells. Vaccine 26:1303–1313PubMedGoogle Scholar
  145. Zhang L, Eisenberg A (1995) Multiple morphologies of crew-cut aggregates of polystyrene-b-poly(acrylic acid) block copolymers. Science 1268:1728–1731Google Scholar
  146. Zou Y, Wu QP, Tansey W, Chow D, Hung MC, Charnsangavej C, Wallace S, Li C (2001) Effectiveness of water soluble poly(L-glutamic acid)–camptothecin conjugate against resistant human lung cancer xenografted in nude mice. Int J Oncol 18:331–336PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Takami Akagi
    • 1
  • Michiya Matsusaki
    • 1
  • Mitsuru Akashi
    • 1
  1. 1.Department of Applied Chemistry, Graduate School of EngineeringOsaka UniversitySuitaJapan

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