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Oral Delivery of Nucleic Acid Drugs

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Oral Delivery of Macromolecular Drugs

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Abstract

Nucleic acid molecules have emerged as versatile tools with promising utility in a variety of biochemical, diagnostic, and therapeutic applications. A parenteral administration of a nucleic acid is inconvenient because of pain, fear, and risks being associated with this type of application. The intestinal epithelium is considered to be an attractive site for oral delivery of therapeutic genes.

The successful development of oral nucleic acid delivery systems is challenged by a variety of barriers encountered with the GI tract. The intestinal mucosa is both a physical and a biochemical barrier, separating the external environment from the internal milieu of the body.

Despite the enormous potential of gene therapy, safe and efficient delivery of nucleic acid into cells is still a dominant task in current biotechnological research. The majority of nucleic acid therapeutics are to a higher degree dependent on delivery systems for successful therapeutic intervention than conventional drugs.

Regarding safety concerns, non-viral gene delivery vehicles that have the required efficiency and safety for use in human gene therapy are being widely investigated as possible alternatives. Non-viral systems show a significantly lower safety risk and can be tailored to specific therapeutic needs.

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References

  • Agrawal, S., X. Zhang, Z. Lu, H. Zhao, J. M. Tamburin, J. Yan, H. Cai, R. B. Diasio, I. Habus and Z. Jiang (1995). Absorption, tissue distribution and in vivo stability in rats of a hybrid antisense oligonucleotide following oral administration. Biochem Pharmacol 50(4): 571–6.

    Article  PubMed  CAS  Google Scholar 

  • Audouy, S., G. Molema, L. de Leij and D. Hoekstra (2000). Serum as a modulator of lipoplex-mediated gene transfection: dependence of amphiphile, cell type and complex stability. J Gene Med 2(6): 465–76.

    Article  PubMed  CAS  Google Scholar 

  • Bernkop-Schnurch, A., C. E. Kast and D. Guggi (2003). Permeation enhancing polymers in oral delivery of hydrophilic macromolecules: thiomer/GSH systems. J Control Release 93(2): 95–103.

    Article  PubMed  CAS  Google Scholar 

  • Bernkop-Schnurch, A., A. H. Krauland, V. M. Leitner and T. Palmberger (2004). Thiomers: potential excipients for non-invasive peptide delivery systems. Eur J Pharm Biopharm 58(2): 253–263.

    Article  PubMed  CAS  Google Scholar 

  • Bernkop-Schnurch, A., H. Zarti and G. F. Walker (2001). Thiolation of polycarbophil enhances its inhibition of intestinal brush border membrane bound aminopeptidase N. J Pharma Sci 90(11): 1907–1914.

    Article  CAS  Google Scholar 

  • Borges, O., G. Borchard, J. C. Verhoef, A. de Sousa and H. E. Junginger (2005). Preparation of coated nanoparticles for a new mucosal vaccine delivery system. Int J Pharm 299(1–2): 155–166.

    Article  PubMed  CAS  Google Scholar 

  • Crooke, S. T. (1998). An overview of progress in antisense therapeutics. Antisense Nucleic Acid Drug Dev 8(2): 115–22.

    Article  PubMed  CAS  Google Scholar 

  • El Ouahabi, A., M. Thiry, V. Pector, R. Fuks, J. M. Ruysschaert and M. Vandenbranden (1997). The role of endosome destabilizing activity in the gene transfer process mediated by cationic lipids. FEBS Lett 414(2): 187–92.

    Article  PubMed  CAS  Google Scholar 

  • Elbashir, S.M., J. Harborth, W. Lendeckel, A. Yalcin, K. Weber and T. Tuschl (2001). Duplexes of 21-nucleotide RNAs mediate RNA inerference in cultured mammalian cells. Nature 411: 494–498.

    Article  PubMed  CAS  Google Scholar 

  • Ellington, A.D. and J. Szostak (1990). In vitro selection of RNA molecules that bind specific ligands. Nature 346: 818–822.

    Article  PubMed  CAS  Google Scholar 

  • Ess, K.C., J.J. Hutton and B.J. Aronow (1994). Double-stranded phosphorothioate oligonucleotide modulation of gene expression. Ann New York Acad Sci 716: 321–332.

    Article  CAS  Google Scholar 

  • Fasano, A. (1998). Novel approaches for oral delivery of macromolecules. J Pharm Sci 87(11): 1351–6.

    Article  PubMed  CAS  Google Scholar 

  • Fire, A., S. Q. Xu, M. K. Montgomery, S. A. Kostas, S. E. Driver and C. C. Mello (1998). Potent and specific genetic interference by double stranded RNA in Caenorhabditis elegans. Nature 391: 806–811.

    Article  PubMed  CAS  Google Scholar 

  • Fraunhofer, W., G. Winter and C. Coester (2004). Asymmetrical flow field-flow fractionation and multiangle light scattering for analysis of gelatin nanoparticle drug carrier systems. Anal Chem 76(7): 1909–20.

    Article  PubMed  CAS  Google Scholar 

  • Gardlik, R., R. Palffy, J. Hodosy, J. Lukacs, J. Turna and P. Celec (2005). Vectors and delivery systems in gene therapy. Med Sci Monit 11(4): RA110–21.

    PubMed  CAS  Google Scholar 

  • Guerrier, T. C., K. Gardiner, T. Marsh, N. Pace and S. Altman (1983). The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35: 849–857.

    Article  Google Scholar 

  • Guggi, D., N. Langoth, M. H. Hoffer, M. Wirth and A. Bernkop-Schnurch (2004). Comparative evaluation of cytotoxicity of a glucosamine-TBA conjugate and a chitosan-TBA conjugate. Int J Pharm 278(2): 353–360.

    Article  PubMed  CAS  Google Scholar 

  • Hacein-Bey-Abina, S., 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 (2003). A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 348(3): 255–6.

    Article  PubMed  Google Scholar 

  • Ishizawa, T., M. Hayashi and S. Awazu (1987). Enhancement of jejunal and colonic absorption of fosfomycin by promoters in the rat. J Pharm Pharmacol 39: 892–895.

    Article  PubMed  CAS  Google Scholar 

  • Johnston, S. A., A. M. Talaat and M. J. McGuire (2002). Genetic immunization: what’s in a name? Arch Med Res 33(4): 325–9.

    Article  PubMed  CAS  Google Scholar 

  • Kai, E. and T. Ochiya (2004). A method for oral DNA delivery with N-acetylated chitosan. Pharmaceutical Res 21(5): 838–843.

    Article  CAS  Google Scholar 

  • Kataoka, K. (1998). [Intracellular gene delivery by polymer micelle vectors]. Nippon Rinsho 56(3): 718–23.

    PubMed  CAS  Google Scholar 

  • Katayose, S. and K. Kataoka (1997). Water-soluble polyion complex associates of DNA and poly(ethylene glycol)-poly(L-lysine) block copolymer. Bioconjug Chem 8(5): 702–7.

    Article  PubMed  CAS  Google Scholar 

  • Kurreck, J., E. Wyszko, C. Gillen and V. A. Erdmann (2002). Design of antisense oligonucleotides stabilized by locked nucleic acids. Nucleic Acids Res 30(9): 1911–8.

    Article  PubMed  CAS  Google Scholar 

  • Lampela, P., J. Raisanen, P. T. Mannisto, S. Yla-Herttuala and A. Raasmaja (2002). The use of low-molecular-weight PEIs as gene carriers in the monkey fibroblastoma and rabbit smooth muscle cell cultures. J Gene Med 4: 205–214.

    Article  PubMed  Google Scholar 

  • Lindmark, T., J. Soderholm, G. Olaison, G. Alvan, G. Ocklind and P. Artursson (1997). Mechanism of absorption enhancement in humans after rectal administration of ampicillin in suppositories containing sodium caprate. Pharm Res 14: 930–935.

    Article  PubMed  CAS  Google Scholar 

  • Loretz, B., F. Foger, M. Werle and A. Bernkop-Schnurch (2006). Oral gene delivery: Strategies to improve stability of pDNA towards intestinal digestion. J Drug Target 14(5): 311–9.

    Article  PubMed  CAS  Google Scholar 

  • Lundstrom, K. and T. Boulikas (2003). Viral and non-viral vectors in gene therapy: technology development and clinical trials. Technol Cancer Res Treat 2: 471–86.

    PubMed  CAS  Google Scholar 

  • Ma, H. and S. L. Diamond (2001). Nonviral gene therapy and its delivery systems. Curr Pharm Biotechnol 2(1): 1–17.

    Article  PubMed  CAS  Google Scholar 

  • Ma, T., D. Hollander, D. Bhalla, H. Nguyen and P. Krugliak (1992). IEC-18, a nontransformed small intestinal cell line for studying epithelial permeability. J Lab Clin Med 120: 329–341.

    PubMed  CAS  Google Scholar 

  • Mansouri, S., Y. Cuie, F. Winnik, Q. Shi, P. Lavigne, M. Benderdour, E. Beaumont and J. C. Fernandes (2006). Characterization of folate-chitosan-DNA nanoparticles for gene therapy. Biomaterials 27(9): 2060–2065.

    Article  PubMed  CAS  Google Scholar 

  • Martien, R., B. Loretz, A.M. Sandbichler and Bernkop Schnürch A (2008). Thiolated chitosan nanoparticles: transfection study in the Caco-2 differentiated cell culture. Nanotechnology 19: 045101 (9 pp).

    Article  PubMed  Google Scholar 

  • Martien, R., B. Loretz, M. Thaler, S. Majzoob and A. Bernkop-Schnurch (2007). Chitosan-thioglycolic acid conjugate: an alternative carrier for oral nonviral gene delivery? J Biomed Mater Res A 82(1): 1–9.

    PubMed  Google Scholar 

  • Mastrobattista, E., W. E. Hennink and R. M. Schiffelers (2007). Delivery of nucleic acids. Pharm Res 24(8): 1561–3.

    Article  PubMed  CAS  Google Scholar 

  • Mastrobattista, E., M. A. van der Aa, W. E. Hennink and D. J. Crommelin (2006). Artificial viruses: a nanotechnological approach to gene delivery. Nat Rev Drug Discov 5(2): 115–21.

    Article  PubMed  Google Scholar 

  • Merdan, T., J. Kopecek and T. Kissel (2002). Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Adv Drug Deliv Rev 54(5): 715–58.

    Article  PubMed  CAS  Google Scholar 

  • Mestecky, J. (1987). The common mucosal immune-system and current strategies for induction of immune-responses in external secretions. J Clin Immunol 7(4): 265–276.

    Article  PubMed  CAS  Google Scholar 

  • Newman, C. M., A. Lawrie, A. F. Brisken and D. C. Cumberland (2001). Ultrasound gene therapy: on the road from concept to reality. Echocardiography 18(4): 339–47.

    Article  PubMed  CAS  Google Scholar 

  • Patil, S. D., D. G. Rhodes and D. J. Burgess (2005). DNA-based therapeutics and DNA delivery systems: a comprehensive review. Aaps J 7(1): E61–77.

    Article  PubMed  CAS  Google Scholar 

  • Raoof, A. A., P. Chiu, Z. Ramtoola, I. K. Cumming, C. Teng, S. P. Weinbach, G. E. Hardee, A. A. Levin and R. S. Geary (2004). Oral bioavailability and multiple dose tolerability of an antisense oligonucleotide tablet formulated with sodium caprate. J Pharm Sci 93(6): 1431–9.

    Article  PubMed  CAS  Google Scholar 

  • Raoof, A. A., Z. Ramtoola, B. McKenna, R. Z. Yu, G. Hardee and R. S. Geary (2002). Effect of sodium caprate on the intestinal absorption of two modified antisense oligonucleotides in pigs. Eur J Pharm Sci 17(3): 131–8.

    Article  PubMed  CAS  Google Scholar 

  • Raper, S. E., N. Chirmule, F. S. Lee, N. A. Wivel, A. Bagg, G. P. Gao, J. M. Wilson and M. L. Batshaw (2003). Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol Genet Metab 80(1–2): 148–58.

    Article  PubMed  CAS  Google Scholar 

  • Riordan, M.L and J. C. Martin (1991). Oligonucleotide based therapeutics. Nature 350: 442–443.

    Article  Google Scholar 

  • Rubanyi, G. M. (2001). The future of human gene therapy. Mol Aspects Med 22(3): 113–42.

    Article  PubMed  CAS  Google Scholar 

  • Sandberg, J. W., C. Lau, M. Jacomino, M. Finegold and S. J. Henning (1994). Improving access to intestinal stem-cells as a step toward intestinal gene-transfer. Human Gene Therapy 5(3): 323–329.

    Article  PubMed  CAS  Google Scholar 

  • Santiago, F. S. and L. M. Khachigian (2001). Nucleic acid based strategies as potential therapeutic tools: mechanistic considerations and implications to restenosis. J Mol Med 79(12): 695–706.

    Article  PubMed  CAS  Google Scholar 

  • Schaffer, D. V., N. A. Fidelman, N. Dan and D. A. Lauffenburger (2000). Vector unpacking as a potential barrier for receptor-mediated polyplex gene delivery. Biotechnol Bioeng 67(5): 598–606.

    Article  PubMed  CAS  Google Scholar 

  • Stein, C. A. (2001). The experimental use of antisense oligonucleotide: a guide for the perplexed. J Clin Invest 108: 641–644.

    PubMed  CAS  Google Scholar 

  • Stull, R. A. and F. C. Szoka, Jr. (1995). Antigene, ribozyme and aptamer nucleic acid drugs: progress and prospects. Pharm Res 12(4): 465–83.

    Article  PubMed  CAS  Google Scholar 

  • Sweetser, D. A., S. M. Hauft, P. C. Hoppe, E. H. Birkenmeier and J. I. Gordon (1988). Transgenic mice containing intestinal fatty acid-binding protein human growth-hormone fusion genes exhibit correct regional and cell-specific expression of the reporter gene in their small-intestine. Proc Natl Acad Sci USA 85(24): 9611–9615.

    Article  PubMed  CAS  Google Scholar 

  • Thomas, M., Q. Ge, J. J. Lu, J. Chen and A. M. Klibanov (2005). Crosslinked small polyethylenimines: while still nontoxic, deliver DNA efficiently to mammalian cells in vitro and in vivo. Pharm. Res 22: 373–380.

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson, E. and A. P. Rolland (1996). Controllable gene therapy – pharmaceutics of non-viral gene delivery systems. J Controlled Release 39(2–3): 357–372.

    Article  CAS  Google Scholar 

  • Tsutsumi, K., S. Li, A. Ghanem, N. Ho and H. WI. (2003). A systematic examination of the in vitro using chamber and the in situ single-pass perfusion model systems in rat ileum permeation of model solutes. J Pharm Sci 92: 344–359.

    Article  PubMed  CAS  Google Scholar 

  • Uherek, C. and W. Wels (2000). DNA-carrier proteins for targeted gene delivery. Adv Drug Deliv Rev 44(2–3): 153–66.

    Article  PubMed  CAS  Google Scholar 

  • van der Aa, M. A., E. Mastrobattista, R. S. Oosting, W. E. Hennink, G. A. Koning and D. J. Crommelin (2006). The nuclear pore complex: the gateway to successful nonviral gene delivery. Pharm Res 23(3): 447–59.

    Article  PubMed  Google Scholar 

  • Yu, J.Y., S.L. DeRuiter and D.L. Turnner (2002). RNA interference by expression of short interferencing and hair pin RNAs in mammalian cells. Proc Natl Acad Sci 99: 6047–6052.

    Article  PubMed  CAS  Google Scholar 

  • Zamecnik, P. C. and M. L. Stephenson (1978). Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proc Natl Acad Sci 75: 280–284.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics, Faculty of Pharmacy, Gadjah Mada University, 55281, Sekip Utara, Yogyakarta, Indonesia

    Ronny Martien

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  1. Ronny Martien
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Correspondence to Ronny Martien .

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  1. Naturwissenschaftliche Fakultät, Universität Innsbruck, Innrain 52, Innsbruck, 6020, Austria

    Andreas Bernkop-Schnürch

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Martien, R. (2009). Oral Delivery of Nucleic Acid Drugs. In: Bernkop-Schnürch, A. (eds) Oral Delivery of Macromolecular Drugs. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0200-9_12

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