Skip to main content
SpringerLink
Log in

Controlled Release of Bioactive Agents in Gene Therapy and Tissue Engineering

  • Chapter
Tissue Engineering, Stem Cells, and Gene Therapies

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 534))

Abstract

Even though the drugs are effective in the treatment of some diseases, they may be inefficient or incapable of solving the problem in some other diseases. It is known that some diseases have genetic causes and therefore the search for a therapy in these cases is intense. The solutions involving either direct application of a gene or its basic product, proteins, especially the growth factors, are oftencontemplated. Gene therapy is a novel approach to treating diseases based on modifying the expression of a person’s genes toward a therapeutic goal. While genes and proteins offer a great opportunity for the treatment of many diseases their administration require critical consideration of the structure and conditions. When the conventional methods of drug administration is adopted for the administration of genes and proteins the results are not successful. Genetic material and the proteins are too labile or unstable due to their fragile 3-D structures and this makes their administration to a medium for long periods in unprotected form impossible. For gene delivery in vivo, additional problems have to be overcome, including the anatomical size constraints, protection from nonspecific interactions with body fluids, extracellular matrix and nontarget cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. BIO, Biotechnology Industry Organization. Biotechnology in Perspective, 1990, “Gene therapy: an overview.” Washington, D.C., Biotechnology IndustryOrganizationhttp://www.gene.com/ae/AB/IWT/GeneTherapyOverview.html

  2. Steiner, J., 2000/1, The genie in the test tube-from gene to gene therapy: part II.Drug Discovery WorldWinter: 55–61.

    Google Scholar 

  3. Guojun, L., 1996http://www.cc.ndsu.nodak.edu/instruct/mcclean/plsc431/students/guojun.htm

  4. Cleland, J.L., Daugherty, A., and Mrsny, R., 2001, Emerging protein delivery methods. Current Opinion in Biotechnology 12, 212–219.

    Article  Google Scholar 

  5. Rose, F.R.A., Oreffo, R.O.C., 2002, Bone tissue engineering: Hope vs hype. Biochemical and Biophysical Research Communications 292: 1–7.

    Article  Google Scholar 

  6. Li, H.R., and Woznet, J.M., 2001, Delivering on the promise of bone morphogenetic proteins. Trends in Biotechnology 19, 255–265.

    Article  Google Scholar 

  7. Musgrave, D. S., Bosch, P., Ghivizzani, S., Robbins, P. D., Evans, C. H., Huard, J., 1999, Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone. Bone 24, 541–547.

    Article  Google Scholar 

  8. Wive!, N., What is gene therapy.http://www.uphs.upenn.edu/ingt

  9. Tanaka, S., 2002, Adenovirus vector-mediated gene transduction for the treatment of bone and joint destrution of rheumatoid arthritis, InTissue Engineering and Biodegradable Equivalents Scientific and Clinical Applications. (Lewandrowski, K., Wise, D.L, Trantolo, D.J,. Gresser, J.D,. Yaszemski, M.J., Altobelli, D.E. Eds.) Marcel Dekker, Inc., N, Y., pp.

    Google Scholar 

  10. Madsen, S.K., and Mooney, D.J., 2000, Delivering DNA with polymer matrices: applications in tissue engineering and gene therapy. PSTT 3, 381–384.

    Google Scholar 

  11. Baltzer, A., Lattermann, C., Whalen, J. D., Braunstein, S., Robbins, P.D., Evans, C. H, 1999, A gene therapy approach to accelerate bone healing. knee surg, Sports Traumatol, Arthrosc. 7, 197–202.

    Google Scholar 

  12. Buyong-Soo, K., Mooney, D.J., 1998, Development of biocompatible synthetic extracellular matrices for tissue engineering. Trends Biotechnol. 16, 197–237.

    Article  Google Scholar 

  13. Beer, S., Hilfinger, J. M., Davidson, B. L., 1997, Extended release of adenovirus from polymer microspheres: potential use in gene therapy for brain tumors. Advanced Drug Delivery Reviews 27, 59–66.

    Article  Google Scholar 

  14. Partridge, K., Yang, X., Clarke, N.M.P., Okubo, Y., Bessho, K., Sebalt, W., Howdle, S. M., Shakesheff, K.M., Oreffo, R. O. C., 2002, Adenoviral BMP-2 gene transfer in mesenchymal stem cells: In vitro and in vivo bone formation on biodegradable polymer scaffolds. Biochemical and Biophysical Research Communications 292, 114–152.

    Article  Google Scholar 

  15. Laurencin, C.T., Attawia, M.A., Lu, L.Q., Borden, M.D., Lu, H.H., Gorum, W.J., Lieberman, J.R., 2001,Poly(lactide-co-glycolide)/hydroxiapatide delivery of BMP-2 producing cells: A regional gene therapy approach to bone regeneration.Biomaterials 22, 1271–1277.

    Article  Google Scholar 

  16. Koltover I., Wagner, K., Safinya C.R., 2000, DNA condensation in two dimensions. Proc. Natl. Acad. Sci. USA 97, 14046–14051.

    Article  Google Scholar 

  17. Sendil, D., Giirsel, t., and Hamel, V., 2000, Preparation of PHBV foams and investigation of their potential for drug release, Tr. J. Medical Sciences 30: 9–14.

    Google Scholar 

  18. Baran E.T, Ozer N, and Hasirci V., 2002, Poly(hydroxybutyrate-co-hydroxyvalerate) nanocapsules as enzyme carriers for cancer therapy: an in vitro study. J Microencapsulation 19, 363–376.

    Article  Google Scholar 

  19. Sendil, D., Wise, D.L., and Hasirci, V., 2002, Assessment of biodegradable controlled release rod systems for pain relief applications. J. Biomaterial Science, Polymer Edition 13, 1–15.

    Google Scholar 

  20. Jeong, B., and Gutowska, A, 2002, Lessons from nature: stimuli-responsive polymers and their biomedical applications. Trends in Biotechnology 20, 305–311.

    Article  Google Scholar 

  21. Kabanov, A.V., 1999, Taking polycation gene delivery system from in vitro to in vivo. Pharm. Sci. Tech. Today 2, 365–372.

    Article  Google Scholar 

  22. Smedt, S. D., Demeester, J., and Hennink, W., 2000, Cationic polymer based gene delivery systems. Pharm. Res. 5, 1425–1433

    Google Scholar 

  23. Kabanov, A.V., Lemieux, P., Vinogradov, S., and Alakhov, V, 2002, Pluronic block copolymers: novel functional molecules for gene therapy. Advanced Drug Delivery Reviews 54, 223–233.

    Article  Google Scholar 

  24. Zhdanov, R.I, Podobed, O.V. and Vlassov, V.V., 2002, Cationic lipid-DNA complexeslipoplexes-for gene transfer and therapy. Bioelectrochemistry 58, 53–64.

    Article  Google Scholar 

  25. Gebhart, C.L., and Kabanov, A.V., 2001, Evaluation of polyplexes as gene transfer agents.J. Controlled Release 73, 401–416.

    Article  Google Scholar 

  26. Yang, X.B., Roach, H.I., Clarke, N.M.P., Howdle, S. M., Quirk, R., Shakesheff, K.M., and Oreffo, R.O.C., 2001, Human osteoprogenitor growth and differentiation on synthetic biodegradable structures after surface modification. Bone 29, 523–531.

    Article  Google Scholar 

  27. Itoh, S., Kikuchi, M., Takakuta, K., Koyama, Y., Matsumoto, H.N., Ichinose, S., Tanaka, J., Kawauchi, T., and Shinomiya, K, 2001, The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagencomposite biomaterial and its function as a carrier of rhBMP-2. J. Biomed. Mater.Res. 54, 445–453.

    Article  Google Scholar 

  28. Tabata, Y., 2000, The importance of drug delivery systems in tissue engineering, Pharm.Sci. Tech. Today 3, 80–89.

    Google Scholar 

  29. Lee, K.Y., Peters, M.C., Anderson, K.W., Mooney, D.C., 2000, Controlled growth factor release from synthetic extracellular matrices. Nature 408, 998–1000.

    Article  Google Scholar 

  30. Howdle, S.M., Watson, M.S., Whitaker, M.J., Popov, V.K., Davies, M.C., Mandel, F.S., Wang, J.D., Shakesheff, K.M, 2001, Supercritical fluid mixing: Preparation of thermally sensitive polymer composites containing bioactive materials. Chem. Commun.7, 109–110.

    Article  Google Scholar 

  31. Bonadio, J., 2000, Tissue engineering via local gene delivery: update and future prospects for enhancing the technology. Advanced Drug Delivery Reviews 44, 185–194.

    Article  Google Scholar 

  32. Kircheis, R., Wightman, L., and Wagner, E, 2001, Design and gene delivery activity of modified polyethylenimines. Advanced Drug Delivery Reviews 53, 341–358.

    Article  Google Scholar 

  33. Fajac, I., Allo, J.C, Souil, E., Merten, M., Pichon, C., Figarella, C., Monsigny, M., Briand, P., and Midoux, P., 2001, Histidylated polylysine as a synthetic vector for gene transfer into immortalized cystic fibrosis airway surface and airway gland. Gene Med. 2, 99–101.

    Google Scholar 

  34. Benns, J.M., Choi, J.S., Mahato, R.I., Park, J.S., and Kim, S.W., 2000, pH-sensitive cationic polymer gene delivery vehicle: N-Ac-poly(L-histidine)-graft-poly(L-lysine) comb shaped polymer, Bioconjug. Chem. 11, 637–645.

    Article  Google Scholar 

  35. Midoux, P., and Monsigny, M., 1999, Efficient gene transfer by histidylated polylysine/pDNA complexes. Bioconjug. Chem. 10, 406–411.

    Article  Google Scholar 

  36. Putnam, D., Gentry, C.A., Pack, D.W., and Langer, R., 2001, Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini. Proc. Natl. Acad. Sci. USA 98, 1200–1205.

    Article  Google Scholar 

  37. Ogris, M., Brunner, S., Schuller, S., Kircheis, R., and Wagner, E., 1999, PEGylated DNA/transferrin-PEI complexes: Reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery. Gene Ther. 6, 595–605.

    Article  Google Scholar 

  38. Nguyen, H.K., Lemieux, P., Viogradov, S.V., Gebhart, C.L., Guerin, N., Paradis, G., Bronich, T.K., Alakhov V.Y, and Kabanov, A.V., 2000, Evaluation of polyetherpolyethyleneimine graft copolymers as gene transfer agents. Gene Ther. 7, 126–138.

    Article  Google Scholar 

  39. Kircheis, R., Wightman, L., Schreiber, A., Robitza, B., Rossler, V., Kursa M., and Wagner, E, 2001, Polyethylenimine/DNA complexes shielded by transferrin target gene expression to tumors after systemic application, Gene Ther. 8, 28–40.

    Article  Google Scholar 

  40. Kopecek, J., Kopeckova, P., Minko, T., and Lu, Z., 2000, HPMA copolymer-anticancer drug conjugates: design, activity, and mechanism of action. Eur. J. Pharm.Biopharm. 50, 61–81.

    Article  Google Scholar 

  41. Merdan, T, Kopecek, J., and Kissel, T., 2002, Prospects for cationic polymers in gene and oligonucleotide therapy against cancer. Advanced Drug Delivery Reviews 54, 715–758.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Engineering Sciences, Biotechnology Research Unit, Middle East Technical University, Ankara, 06531, Turkey

    Dilek Şendil Keskin

  2. Department of Biological Sciences, Biotechnology Research Unit, Middle East Technical University, Ankara, 06531, Turkey

    Vasif Hasirci

Authors
  1. Dilek Şendil Keskin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vasif Hasirci
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Science Faculty and Biotechnology Institute, Ankara University, Ankara, Turkey

    Y. Murat Elçin

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Keskin, D.Ş., Hasirci, V. (2003). Controlled Release of Bioactive Agents in Gene Therapy and Tissue Engineering. In: Elçin, Y.M. (eds) Tissue Engineering, Stem Cells, and Gene Therapies. Advances in Experimental Medicine and Biology, vol 534. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0063-6_21

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0063-6_21

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4907-5

  • Online ISBN: 978-1-4615-0063-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation