Pharmaceutical Research

, Volume 24, Issue 4, pp 618–627

Encapsulation of Nucleic Acids and Opportunities for Cancer Treatment

  • Lisa Brannon-Peppas
  • Bilal Ghosn
  • Krishnendu Roy
  • Kenneth Cornetta
Expert Review

Abstract

The development of nucleic acid drugs for the treatment of various cancers has shown great promise in recent years. However, efficient delivery of these drugs to target cells remains a significant challenge towards the successful development of such therapies. This review provides a comprehensive overview of encapsulation technologies being developed for the delivery of nucleic acid-based anti-cancer agents. Both micro and nanoparticles systems are discussed along with their use in delivering plasmid DNA as well as oligonucleotides. The majority of the systems discussed have used DNA immunotherapy as the potential mode of anticancer therapy, which requires targeting to antigen presenting cells. Other applications, including those with oligonucleotides, focus on targeting tumor cells directly. The results obtained so far show the excellent promise of encapsulation as an efficient means of delivering therapeutic nucleic acids.

Key words

encapsulation cancer DNA gene particles 

References

  1. 1.
    C. V. A. Wynter. The dialectics of cancer: a theory of the initiation and development of cancer through errors in siRNA. Med. Hypotheses 66:612–635 (2006).PubMedCrossRefGoogle Scholar
  2. 2.
    P. T. Reiger. The biology of cancer genetics. Sem. Oncol. Nurs. 20:145–154 (2004).CrossRefGoogle Scholar
  3. 3.
    R. K. Jain. Barriers to drug delivery in solid tumors. Sci. Am. 271:58–65 (1994).PubMedCrossRefGoogle Scholar
  4. 4.
    R. K. Jain. Transport of molecules, particles and cells in solid tumors. Annu. Rev. Biomed. Eng. 1:241–263 (1999).PubMedCrossRefGoogle Scholar
  5. 5.
    R. K. Jain. Delivery of molecular medicine to solid tumors: lessons from in vivo imaging of gene expression and function. J. Control. Release 74:7–25 (2001).PubMedCrossRefGoogle Scholar
  6. 6.
    R. K. Jain. Delivery of molecular and cellular medicine to solid tumors. Adv. Drug Deliv. Rev. 46:149–168 (2001).PubMedCrossRefGoogle Scholar
  7. 7.
    C. Pozrikidis and D. A. Farrow. A model of fluid flow in solid tumors. Ann. Biomed. Eng. 31:181–194 (2003).PubMedCrossRefGoogle Scholar
  8. 8.
    M. J. Hawkins, J. R. Lane, L. Harris, P. J. Williams, V. Trieu, P. Soon-Shiong, and N. Desai. Comparative pharmacokinetic (pk) study of a cremophor-free, protein stabilized, nanoparticle formulation (abi-007) and a cremophor-based formulation of paclitaxel (p) in patients with advanced solid tumors. Eur. J. Cancer Suppl. 2:164 (2004).CrossRefGoogle Scholar
  9. 9.
    Z. Xu, W. Gu, J. Huang, H. Sui, Z. Zhou, Y. Yang, Z. Yan, and Y. Li. In vitro and in vivo evaluation of actively targetable nanoparticles for paclitaxel delivery. Int. J. Pharm. 288:361–368 (2005).PubMedCrossRefGoogle Scholar
  10. 10.
    H. Miura, H. Onishi, M. Sasatsu, and Y. Machida. Antitumor characteristics of methoxypolyethylene glycol-poly(-lactic acid) nanoparticles containing camptothecin. J. Control. Release 97:101–113 (2004).PubMedCrossRefGoogle Scholar
  11. 11.
    J. Hyung Park, S. Kwon, M. Lee, H. Chung, J.-H. Kim, Y.-S. Kim, R.-W. Park, I.-S. Kim, S. Bong Seo, I. C. Kwon, and S. Young Jeong. Self-assembled nanoparticles based on glycol chitosan bearing hydrophobic moieties as carriers for doxorubicin: in vivo biodistribution and anti-tumor activity. Biomaterials 27:119–126 (2006).PubMedCrossRefGoogle Scholar
  12. 12.
    S. A. Rosenberg, P. M. Aebersold, K. Cornetta, A. Kasid, R. A. Morgan, R. Moen, E. M. Karson, M. T. Lotze, J. C. Yang, S. L. Topalian, M. H. Merino, K. Culver, A. D. Miller, M. D. Blaese, and W. F. Anderson. Gene transfer into humans-immunotherapy of patients with advanced melanoma, using tumor infiltrating lymphocytes modified by retroviral gene transduction. N. Engl. J. Med. 323:570–578 (1990).PubMedCrossRefGoogle Scholar
  13. 13.
    A. El-Aneed. Current strategies in cancer gene therapy. Eur. J. Pharmacol. 498:1–8 (2004).PubMedCrossRefGoogle Scholar
  14. 14.
    T. Niidomeand and L. Huang. Gene therapy progress and prospects: non-viral vectors. Gene Ther. Wkly. 9:1647–1652 (2002).CrossRefGoogle Scholar
  15. 15.
    S. E. Raper, N. Chirmule, F. S. Lee, N. A. Wivel, A. Bagg, G. P. Gao, J. M. Wilson, and M. L. Batshaw. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Molec. Genet. Metab. 80:148–158 (2003).CrossRefPubMedGoogle Scholar
  16. 16.
    A. Berns. Good news for gene therapy. N. Engl. J. Med. 350:1679–1680 (2004).PubMedCrossRefGoogle Scholar
  17. 17.
    S. Hacein-Bey-Abina, C. von Kalle, M. Schmidt, F. Le Deist, N. Wulffraat, E. McIntyre, I. Radford, J. L. Villeval, C. C. Fraser, M. Cavazzana-Calvo, and A. Fischer. A serious adverse event after successful gene therapy for x-linked severe combined immunodeficiency. N. Engl. J. Med. 348:255–256 (2003).PubMedCrossRefGoogle Scholar
  18. 18.
    Y. Kaneda and Y. Tabata. Non-viral vectors for cancer therapy. Cancer Sci. 97:348–354 (2006).PubMedCrossRefGoogle Scholar
  19. 19.
    G. Kaul and M. Amiji. Tumor-targeted gene delivery using poly(ethylene glycol)-modified gelatin nanoparticles: in vitro and in vivo studies. Pharm. Res. 22:951–961 (2005).PubMedCrossRefGoogle Scholar
  20. 20.
    D. W. Pack, A. S. Hoffman, S. Pun, and P. S. Stayton. Design and development of polymers for gene delivery. Nat. Rev., Drug Discov. 4:581–593 (2005).CrossRefGoogle Scholar
  21. 21.
    R. A. Jain. The manufacturing techniques of various drug loaded biodegradable poly(lactide-co-glycolide) (PLGA) devices. Biomaterials 21:2475–2490 (2000).PubMedCrossRefGoogle Scholar
  22. 22.
    D. T. Birnbaum, J. D. Kosmala, and L. Brannon-Peppas. Optimization of preparation techniques for poly(lactic acid-co-glycolic acid) nanoparticles. J. Nanopart. Res. 2:173–181 (2000).CrossRefGoogle Scholar
  23. 23.
    F. Fawaz, F. Bonini, M. Guyot, A.-M. Lagueny, H. Fessi, and J.-P. Devissaguet. Influence of poly(dl-lactide) nanocapsules on the biliary clearance and enterohepatic circulation of indomethacin in the rabbit. Pharm. Res. 10:750–756 (1993).PubMedCrossRefGoogle Scholar
  24. 24.
    P. D. Scholes, A. G. A. Coombes, L. Illum, S. S. Davis, M. Vert, and M. C. Davies. The preparation of sub-200 nm poly(lactide-co-glycolide) microspheres for site-specific drug delivery. J. Control. Release 25:145–153 (1993).CrossRefGoogle Scholar
  25. 25.
    H. Maeda, J. Wu, T. Sawa, Y. Matsumura, and K. Hori. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Control. Release 65:271–284 (2000).PubMedCrossRefGoogle Scholar
  26. 26.
    B. Stella, S. Arpicco, M. T. Peracchia, D. Desmaele, J. Hoebeke, M. Renoir, J. D’Angelo, L. Cattel, and P. Couvreur. Design of folic acid-conjugated nanoparticles for drug targeting. J. Pharm. Sci. 89:1452–1464 (2000).PubMedCrossRefGoogle Scholar
  27. 27.
    G. Russell-Jones, K. McTavish, J. McEwan, J. Rice, and D. Nowotnik. Vitamin-mediated targeting as a potential mechanism to increase drug uptake by tumours. J. Inorg. Biochem. 98:1625–1633 (2004).PubMedCrossRefGoogle Scholar
  28. 28.
    J. Jo, M. Yamamoto, K. Matsumoto, T. Nakamura, and Y. Tabata. Liver targeting of plasmid DNA with a cationized pullulan for tumor suppression. J. Nanosci. Nanotech. 6:2853–2859 (2006).CrossRefGoogle Scholar
  29. 29.
    S. Krasnici, A. Werner, M. Eichhorn, M. Schmitt-Sody, S. Pahernik, B. Sauer, B. Schulze, M. Teifel, U. Michaelis, K. Naujoks, and M. Dellian. Effect of the surface charge of liposomes on their uptake by angiogenic tumor vessels. Int. J. Cancer 105:561–567 (2003).PubMedCrossRefGoogle Scholar
  30. 30.
    M. C. Woodleand and P. Y. Lu. Nanoparticles deliver rnai therapy. Nanotoday August 8:34–41 (2005).Google Scholar
  31. 31.
    A. V. Harpe, H. Petersen, Y. Li, and T. Kissel. Characterization of commercially available and synthesized polyethylenimines for gene delivery. J. Control. Release 69:309–322 (2000).CrossRefGoogle Scholar
  32. 32.
    S. Kawakami, S. Fumoto, M. Nishikawa, F. Yamashita, and M. Hashida. In vivo gene delivery to the liver using novel galactosylated cationic liposomes. Pharm. Res. 17:306–313 (2000).PubMedCrossRefGoogle Scholar
  33. 33.
    P. Lemieux, S. V. Vinogradov, C. L. Gebhart, N. Guerin, G. Paradis, H.-K. Nguyen, B. Ochietti, Y. G. Suzdaltseva, E. V. Bartakova, T. K. Bronich, Y. St.-Pierre, V. Y. Alakhov, and A. V. Kabanov. Block and graft copolymers and nanogel copolymer networks for DNA delivery into cell. J. Drug Target. 8:91–105 (2000).PubMedGoogle Scholar
  34. 34.
    Y.-B. Lim, S.-O. Han, H.-U. Kong, Y. Lee, J.-S. Park, B. Jeong, and S. W. Kim. Biodegradable polyester, poly(alpha-(4-aminobutyl)-l-glycolic acid), as a non-toxic gene carrier. Pharm. Res. 17:811–816 (2000).PubMedCrossRefGoogle Scholar
  35. 35.
    E. G. Saravolac, O. Ludkovski, R. Skirrow, M. Ossanlou, Y. P. Zhang, C. Giesbrecht, J. Thompson, S. Thomas, H. Stark, P. R. Cullis, and P. Scherrer. Encapsulation of plasmid DNA in stabilized plasmid-lipid particles composed of different cationic lipid concentration for optimal transfection activity. J. Drug Target. 7:423–437 (2000).PubMedCrossRefGoogle Scholar
  36. 36.
    E. Schacht, V. Toncheva, L. D. Kie, and P. Dubruel. Synthetic polymers as vectors for gene delivery. Polym Prepr (Am Chem Soc, Div Polym Chem) 41:1609–1610 (2000).Google Scholar
  37. 37.
    S. W. Yi, T. Y. Yune, T. W. Kim, H. Chung, Y. W. Choi, I. C. Kwon, E. B. Lee, and S. Y. Joeng. A cationic lipid emulsion/DNA complex as a physically stable and serum-resistant gene delivery system. Pharm. Res. 17:314–320 (2000).PubMedCrossRefGoogle Scholar
  38. 38.
    N. Shi, R. J. Boado, and W. M. Pardridge. Receptor-mediated gene targeting to tissues in vivo following intravenous administration of pegylated immunoliposomes. Pharm. Res. 18:1091–1095 (2001).PubMedCrossRefGoogle Scholar
  39. 39.
    P. Dubruel, B. Christiaens, B. Vanloo, K. Bracke, M. Rosseneu, J. Vandekerckhove, and E. Schacht. Physcichemical and biological evaluation of cationic polymethacrylates as vectors for gene delivery. Eur. J. Pharm. Sci. 18:211–220 (2003).PubMedCrossRefGoogle Scholar
  40. 40.
    T. Hao, U. McKeever, and M. L. Hedley. Biological potency of microsphere encapsulated plasmid DNA. J. Control. Release 69:249–259 (2000).PubMedCrossRefGoogle Scholar
  41. 41.
    L. Lunsford, U. McKeever, V. Eckstein, and M. L. Hedley. Tissue distribution and persistence in mice of plasmid DNA encapsulated in a PLGA-based microsphere delivery vehicle. J. Drug Target. 8:39–50 (2000).PubMedGoogle Scholar
  42. 42.
    A. M. Tinsley-Bown, R. Fretwell, A. B. Dowsett, S. L. Davis, and G. H. Farrar. Formulation of poly(d,l-lactic-co-glycolic acid) microparticles for rapid plasmid DNA delivery. J. Control. Release 66:229–241 (2000).PubMedCrossRefGoogle Scholar
  43. 43.
    M. Stern, K. Ulrich, D. M. Geddes, and E. W. Alton. Poly (d, l-lactide-co-glycolide)/DNA microspheres to facilitate prolonged transgene expression in airway epithelium in vitro, ex vivo and in vivo. Gene Therapy 10:1282–1288 (2003).PubMedCrossRefGoogle Scholar
  44. 44.
    S. R. Little, D. M. Lynn, Q. Ge, D. G. Anderson, S. V. Puram, J. Chen, H. N. Eisen, and R. Langer. Poly-beta amino ester-containing microparticles enhance the activity of nonviral genetic vaccines. Proc. Natl. Acad. Sci. USA. 101:9534–9539 (2004).PubMedCrossRefGoogle Scholar
  45. 45.
    E. Walter, D. Dreher, M. Kok, L. Thiele, S. G. Kiama, P. Gehr, and H. P. Merkle. Hydrophilic poly(dl-lactide-co-glycolide) microspheres for the delivery of DNA to human-derived macrophages and dendritic cells. J. Control. Release 76:149–168 (2001).PubMedCrossRefGoogle Scholar
  46. 46.
    E. Walter, L. Thiele, and H. P. Merkle. Gene delivery systems to phagocytic antigen-presenting cells. STP Pharma. Sci. 11:45–56 (2001).Google Scholar
  47. 47.
    E. Walter, K. Moelling, J. Pavlovic, and H. P. Merkle. Microencapsulation of DNA using poly(dl-lactide-co-glycolide): stability issues and release characteristics. J. Control. Release 61:361–374 (1999).PubMedCrossRefGoogle Scholar
  48. 48.
    U. McKeever, S. Barman, T. Hao, P. Chambers, S. Song, L. Lunsford, Y. Hsu, K. Roy, and M. Hedley. Protective immune responses elicited in mice by immunization with formulations of poly(lactide-co-glycolide) microparticles. Vaccine. 20:1524–1531 (2002).PubMedCrossRefGoogle Scholar
  49. 49.
    S. L. Goh, N. Murthy, M. Xu, and J. M. Frechet. Cross-linked microparticles as carriers for the delivery of plasmid DNA for vaccine development. Bioconjug. Chem. 15:67–74 (2004).CrossRefGoogle Scholar
  50. 50.
    S. P. Kasturi, K. Sachaphibulkij, and K. Roy. Covalent conjugation of polyethyleneimine on biodegradable microparticles for delivery of plasmid DNA vaccines. Biomaterials 26:6375–6385 (2005).PubMedCrossRefGoogle Scholar
  51. 51.
    G. Lambert, E. Fattal, and P. Couvreur. Nanoparticulate systems for the delivery of antisense oligonucleotides. Adv. Drug Deliv. Rev. 47:99–112 (2001).PubMedCrossRefGoogle Scholar
  52. 52.
    J. M. Benns and S. W. Kim. Tailoring new gene delivery designs for specific targets. J. Drug Target. 8:1–12 (2000).PubMedCrossRefGoogle Scholar
  53. 53.
    G. Giammona, G. Cavallaro, G. Pitarresi, and E. Pedone. Novel polyaminoacidic copolymers as nonviral gene vectors. Colloid Polym. Sci. 278:69–73 (2000).CrossRefGoogle Scholar
  54. 54.
    S. Ohashi, T. Kubo, T. Ikeda, Y. Arai, K. Takahashi, Y. Hirasawa, M. Takigawa, E. Satoh, J. Imanishi, and O. Mazda. Cationic polymer-mediated genetic transduction into cultured human chondrosarcoma-derived hcs-2/8 cells. J. Orthop. Sci. 6:75–81 (2001).PubMedCrossRefGoogle Scholar
  55. 55.
    W. Suh, S.-O. Han, L. Yu, and S. W. Kim. An angiogenic, endothelial-cell-targeted polymeric gene carrier. Mol. Ther. 6:664–672 (2002).PubMedCrossRefGoogle Scholar
  56. 56.
    J. Panyam and V. Labhasetwar. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv. Drug Deliv. Rev. 55:329–347 (2003).PubMedCrossRefGoogle Scholar
  57. 57.
    S.-O. Han, R. I. Mahato, Y. K. Sung, and S. W. Kim. Development of biomaterials for gene therapy. Mol. Ther. 2:302–317 (2000).PubMedCrossRefGoogle Scholar
  58. 58.
    M. E. Davis. Non-viral gene delivery systems. Curr. Opin. Biotechnol. 13:128–131 (2002).PubMedCrossRefGoogle Scholar
  59. 59.
    T. Merdan, J. Kopecek, and T. Kissel. Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Adv. Drug Deliv. Rev. 54:715–758 (2002).PubMedCrossRefGoogle Scholar
  60. 60.
    A. Vila, A. Sanchez, C. Perez, and M. J. Alonso. PLA-PAG nanospheres: New carriers for transmucosal delivery of proteins and plasmid DNA. Polym. Adv. Technol. 13:851–858 (2002).CrossRefGoogle Scholar
  61. 61.
    G. G. d. Barrio, F. J. Novo, and J. M. Irache. Loading of plasmid DNA into PLGA microparticles using TROMS (total recirculation one-machine system): evaluation of its integrity and controlled release properties. J. Control. Release 86:123–130 (2003).PubMedCrossRefGoogle Scholar
  62. 62.
    S. Rhaese, H. v. Briesen, H. Rubsamen-Waigmann, J. Kreuter, and K. Langer. Human serum albumin-polyethylenimine nanoparticles for gene delivery. J. Control. Release 92:199–208 (2003).PubMedCrossRefGoogle Scholar
  63. 63.
    S. Prabha and V. Labhasetwar. Critical determinants in PLGA/PLA nanoparticle-mediated gene expression. Pharm. Res. 21:354–364 (2004).PubMedCrossRefGoogle Scholar
  64. 64.
    S. Hirosue, B. G. Müller, R. C. Mulligan, and R. Langer. Plasmid DNA encapsulation and release from solvent diffusion nanospheres. J. Control. Release 70:231–242 (2001).PubMedCrossRefGoogle Scholar
  65. 65.
    Y. Liu and X. Deng. Influences of preparation conditions on particle size and DNA-loading efficiency for poly(dl-lactic acid-polyethylene glycol) microspheres entrapping free DNA. J. Control. Release 83:147–155 (2002).PubMedCrossRefGoogle Scholar
  66. 66.
    C. Perez, A. Sanchez, D. Putman, D. Ting, R. Langer, and M. J. Alonso. Poly(lactic acid)-poly)ethylene glycol) nanoparticles as new carriers for the delivery of plasmid DNA. J. Control. Release 75:211–224 (2001).PubMedCrossRefGoogle Scholar
  67. 67.
    M. Sandor, S. Mehta, J. Harris, C. Thanos, P. Weston, J. Marshall, and E. Mathiowitz. Transfection of hek cells via DNA-loaded PLGA and p(FASA) nanospheres. J. Drug Target. 10:497–506 (2002).PubMedCrossRefGoogle Scholar
  68. 68.
    S. Ando, D. Putnam, D. W. Pack, and R. Langer. Plga microspheres containing plasmid DNA: preservation of supercoiled DNA via cryopreparation and carbohydrate stabilization. J. Pharm. Sci. 88:126–130 (1999).PubMedCrossRefGoogle Scholar
  69. 69.
    J. H. Jeong, S. W. Kim, and T. G. Park. Biodegradable triblock copolymer of PLGA-PEG-PLGA enhances gene transfection efficiency. Pharm. Res. 21:50–54 (2004).PubMedCrossRefGoogle Scholar
  70. 70.
    S. Mansouri, P. Lavigne, K. Corsi, M. Benderdour, E. Beaumont, and J. C. Fernandes. Chitosan-DNA nanoparticles as non-viral vectors in gene therapy: strategies to improve transfection efficacy. Eur. J. Pharm. Biopharm. 57:1–8 (2004).PubMedCrossRefGoogle Scholar
  71. 71.
    H. Mao, K. Roy, V. Troung-Le, K. Janes, K. Lin, Y. Wang, J. August, and K. Leong. Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and transfection efficiency. J. Control. Release 70:399–421 (2001).PubMedCrossRefGoogle Scholar
  72. 72.
    K. Roy, H. Mao, S. Huang, and K. Leong. Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nat. Med. 5:387–391 (1999).PubMedCrossRefGoogle Scholar
  73. 73.
    A. Bozkir and I. M. Saka. Chitosan nanoparticles for plasmid DNA delivery: effect if chitosan molecular structure on formulation and release characteristics. Drug Deliv. 11:107–112 (2004).PubMedCrossRefGoogle Scholar
  74. 74.
    M. N. V. R. Kumar, U. Bakowsky, and C. M. Lehr. Preparation and characterization of cationic PLGA nanospheres as DNA carriers. Biomaterials 25:1771–1777 (2004).CrossRefGoogle Scholar
  75. 75.
    U. Galderisi, A. Cascino, and A. Giordano. Antisense oligonucleotides as therapeutic agents. J. Cell Physiol. 181:251–257 (1999).PubMedCrossRefGoogle Scholar
  76. 76.
    C. Chavany, Y. Connell, and L. Neckers. Contribution of sequence and phosphorothioate content to inhibition of cell growth and adhesion caused by c-myc antisense oligomers. Mol. Pharmacol. 48:736–746 (1995).Google Scholar
  77. 77.
    B. P. Monia, J. F. Johnston, T. Geiger, M. Muller, and D. Fabbro. Antitumor activity of a phosphorothioate antisense oligodeoxynucleotide targeted against c-raf kinase. Nat. Med. 2:668–675 (1996).PubMedCrossRefGoogle Scholar
  78. 78.
    M. D. deSmet, C. J. Meenken, and G. J. v. d. Horn. Fomivirsen—a phosphorothioate oligonucleotide for the treatment of cmv retinitis. Ocul. Immunol. Inflamm. 7:189–198 (1999).CrossRefGoogle Scholar
  79. 79.
    M. Butler and K. Stecker. Cellular distribution of phosphorothioate oligodeoxynucleotides in normal rodent tissues. Lab. Invest. 77:379–388 (1997).PubMedGoogle Scholar
  80. 80.
    R. Z. Yu and J. Q. Su. Prediction of clinical responses in a simulated phase III trial of Crohn’s patients administered the antisense phosphorothioate oligonucleotide ISIS 2302: comparison of proposed dosing regimens. Antisense Nucleic Acid Drug Dev. 13:57–66 (2003).PubMedCrossRefGoogle Scholar
  81. 81.
    S. M. Elbashir, J. Harborth, W. Lendeckel, A. Yalcin, K. Weber, and T. Tuschl. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411:494–498 (2001).PubMedCrossRefGoogle Scholar
  82. 82.
    R. L. Juliano, S. Alahari, H. Yoo, R. Kole, and M. Cho. Antisense pharmacodynamics: critical issues in the transport and delivery of antisense oligonucleotides. Pharm. Res. 16:494–502 (1999).PubMedCrossRefGoogle Scholar
  83. 83.
    C. J. Marcus-Sekura, A. M. Woerner, K. Shinozuka, G. Zon, and G. V. Quinnan. Comparative inhibition of chloramphenicol acetyltransferase gene expression by antisense oligonucleotides analogues having alkyl phosphotriester, methylphosphonate and phosphorothioate linkages. Nucleic Acids Res. 15:5749–5763 (1987).PubMedCrossRefGoogle Scholar
  84. 84.
    A. C. Kilic, Y. Capan, I. Vural, R. N. Gursoy, T. Dalkara, A. Cuine, and A. A. Hincal. Preparation and characterization of PLGA nanospheres for the targeted delivery of nr2b-specific antisense oligonucleotides to the nmda receptors in the brain. J. Microencapsul 22:633–641 (2005).PubMedCrossRefGoogle Scholar
  85. 85.
    G. Lambert, J. R. Bertrand, E. Fattal, F. Subra, H. Pinto-Alphandary, C. Malvy, C. Auclair, and P. Couvreur. Ews fli-1 antisense nanocapsules inhibits Ewing sarcoma-related tumor in mice. Biochem. Biophys. Res. Commun. 279:401–406 (2000).PubMedCrossRefGoogle Scholar
  86. 86.
    A. J. Hollins, M. Benboubetra, Y. Omidi, B. H. Zinselmeyer, A. G. Schatzlein, I. F. U. IF, and S. Akhtar. Evaluation of generation 2 and 3 poly(propylenimine) dendrimers for the potential cellular delivery of antisense oligonucleotides targeting the epidermal growth factor receptor. Pharm. Res. 21:458–466 (2004).PubMedCrossRefGoogle Scholar
  87. 87.
    L. M. Santhakumaran, T. Thomas, and T. J. Thomas. Enhanced cellular uptake of a triplex-forming oligonucleotide by nanoparticle formation in the presence of polypropylenimine dendrimers. Nucleic Acids Res. 32:2102–2112 (2004).PubMedCrossRefGoogle Scholar
  88. 88.
    D. Lochmann, J. Weyermann, C. Georgens, R. Prassl, and A. Zimmer. Albumin-protamine-oligonucleotide nanoparticles as a new antisense delivery system. Part 1: physicochemical characterization. Eur. J. Pharm. Biopharm. 59:419–429 (2005).PubMedCrossRefGoogle Scholar
  89. 89.
    J. Weyermann, D. Lochmann, C. Georgens, and A. Zimmer. Albumin-protamine-oligonucleotide-nanoparticles as a new antisense delivery system. Part 2: cellular uptake and effect. Eur. J. Pharm. Biopharm. 59:431–438 (2005).PubMedCrossRefGoogle Scholar
  90. 90.
    J. H. Seong, K. M. Lee, S. T. Kim, S. E. Jin, and C. K. Kim. Polyethylenimine-based antisense oligodeoxynucleotides of il-4 suppress the production of il-4 in a murine model of airway inflammation. J. Gene Med. 8:314–323 (2006).PubMedCrossRefGoogle Scholar
  91. 91.
    S. Gao, J. Chen, L. Dong, Z. Ding, Y. H. Yang, and J. Zhang. Targeting delivery of oligonucleotide and plasmid DNA to hepatocyte via galactosylated chitosan vector. Eur. J. Pharm. Biopharm. 60:327–334 (2005).PubMedCrossRefGoogle Scholar
  92. 92.
    S. P. Kasturi, H. Qin, K. S. Thomson, S. El-Bereir, S. C. Cha, S. Neelapu, L. W. Kwak, and K. Roy. Prophylactic anti-tumor effects in a b cell lymphoma model with DNA vaccines delivered on polyethylenimine (PEI) functionalized PLGA microparticles. J. Control. Release 113:261–270 (2006).CrossRefGoogle Scholar
  93. 93.
    A. Maheshwari, R. I. Mahato, J. McGregor, S. Han, W. E. Samlowski, J. S. Park, and S. W. Kim. Soluble biodegradable polymer-based cytokine gene delivery for cancer treatment. Mol. Ther. 2:121–130 (2000).PubMedCrossRefGoogle Scholar
  94. 94.
    R. M. Schiffelers, A. Ansari, J. Xu, Q. Zhou, Q. Tang, G. Storm, G. Molema, P. Y. Lu, P. V. Scaria, and M. C. Woodle. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res. 32:e149 (2004).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Lisa Brannon-Peppas
    • 1
  • Bilal Ghosn
    • 2
  • Krishnendu Roy
    • 2
  • Kenneth Cornetta
    • 3
  1. 1.Department of Biomedical Engineering and College of PharmacyThe University of Texas at AustinAustinUSA
  2. 2.Department of Biomedical EngineeringThe University of Texas at AustinAustinUSA
  3. 3.Department of Medical and Molecular GeneticsIndiana University School of MedicineIndianapolisUSA

Personalised recommendations