Skip to main content
SpringerLink
Log in

Enzyme-Promoted Degradation of Polymeric Matrices for Controlled Drug Delivery: Analytical Model and Numerical Simulations

  • Chapter
  • First Online:
Degradation of Implant Materials

Abstract

Controlled drug delivery is one of the main avenues along which the multibillion dollar pharmaceutical industry is concentrating its efforts today. This emphasis is dictated by attempts to improve therapy efficiency and patient compliance, as well as by most stringent economic constraints.

This chapter presents the design of an implantable, degradable, drug delivery device, the function of which is controlled by the concentration and activity of a given enzyme present at the site of implantation. Also, using an appropriately developed analytical model, the performance of this device is assessed in terms of its geometrical characteristics and functional parameters. The engineering procedures thus developed provide the efficient tools required for both the rational design and performance analysis of such devices.

This chapter is taken in part from the M.Sc. thesis of Tomer Gold, submitted to the Senate of the Technion—Israel Institute of Technology, in 2001.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

References

  1. Reed AM, Gilding DK (1981) Biodegradable polymers for use in surgery—Poly(glycolic)-poly(lactic acid) Homo and co-polymers.2. In vitro degradation. Polymer 22:494–498

    Article  CAS  Google Scholar 

  2. Shive MS, Anderson JM (1997) Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 28:5–24

    Article  Google Scholar 

  3. Heller J, Hoffman AS (2004) Drug delivery systems. In: Ratner BD, Hoffman AS, Schoen FJ, Lemons JE (eds) Biomaterials science, an introduction to materials in medicine, 2nd edn. Elsevier Academic, Amsterdam

    Google Scholar 

  4. Wischke C, Schwendeman SP (2008) Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm 364(2):298–327

    Article  CAS  Google Scholar 

  5. Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces 75:1–18

    Article  CAS  Google Scholar 

  6. Giteau A, Venier-Julienne MC, Aubert-Pouëssel A, Benoit JP (2008) How to achieve sustained and complete protein release from PLGA-based microparticles? Int J Pharm 350(1–2):14–26

    Article  CAS  Google Scholar 

  7. Mohamed F, Van der Walle C (2008) Engineering biodegradable polyester particles with specific drug targeting and drug release properties. J Pharm Sci 97(1):71–87

    Article  CAS  Google Scholar 

  8. Benny O, Menon LG, Gilert A, Goren E, Kim SK, Stewman C, Black PM, Carroll RS, Machluf M (2009) Local delivery of polylactic-co-glycolic acid microspheres containing Imatinib mesylate inhibits intracranial xenograft glioma growth. Clin Cancer Res 15:1222–1231

    Article  CAS  Google Scholar 

  9. Bobo WV, Shelton RC (2010) Risperidone long-acting injectable (Risperdal Consta®) for maintenance treatment in patients with bipolar disorder. Expert Rev Neurother 10(11):1637–1658

    Article  CAS  Google Scholar 

  10. Brem H, Kader A, Epstein JI, Tamargo RJ, Domb A, Langer R, Leong KW (1989) Biocompatibility of a biodegradable, controlled-release polymer in the rabbit brain. Sel Cancer Ther 5(2):55–65

    Article  CAS  Google Scholar 

  11. Attenello FJ, Mukherjee D, Datoo G, McGirt MJ, Bohan E, Weingart JD, Olivi A, Quinones-Hinojosa A, Brem H (2008) Use of Gliadel (BCNU) wafer in the surgical treatment of malignant glioma: a 10-year institutional experience. Ann Surg Oncol 15(10):2887–2893

    Article  Google Scholar 

  12. Göpferich A, Tessmar J (2002) Polyanhydride degradation and erosion. Adv Drug Deliv Rev 54(7):911–931

    Article  Google Scholar 

  13. Heller J, Barr J, Ng SY, Abdellauoi KS, Gurny R (2002) Poly(ortho esters): synthesis, characterization, properties and uses. Adv Drug Deliv Rev 54(7):1015–1039

    Article  CAS  Google Scholar 

  14. Eng NF, Garlapati S, Gerdts V, Potter A, Babiuk LA, Mutwiri GK (2010) The potential of polyphosphazenes for delivery of vaccine antigens and immunotherapeutic agents. Curr Drug Deliv 7(1):13–20

    Article  CAS  Google Scholar 

  15. Lakshmi S, Katti DS, Laurencin CT (2003) Biodegradable polyphosphazenes for drug delivery applications. Adv Drug Deliv Rev 55(4):467–482

    Article  CAS  Google Scholar 

  16. Körber M (2010) PLGA erosion: solubility- or diffusion-controlled? Pharm Res 27(11):2414–2420

    Article  Google Scholar 

  17. Katz JS, Zhong S, Ricart BG, Pochan DJ, Hammer DA, Burdick JA (2010) Modular synthesis of biodegradable diblock copolymers for designing functional polymersomes. J Am Chem Soc 132(11):3654–3655

    Article  CAS  Google Scholar 

  18. Bawa P, Pillay V, Choonara YE, du Toit LC (2009) Stimuli-responsive polymers and their applications in drug delivery. Biomed Mater 4(2):22001

    Article  Google Scholar 

  19. Miyata T, Uragami T, Nakamae K (2002) Biomolecule-sensitive hydrogels. Adv Drug Deliv Rev 54(1):79–98

    Article  CAS  Google Scholar 

  20. Qiu Y, Park K (2001) Environment-sensitive hydrogels for drug delivery. Adv Drug Deliv Rev 53(3):321–339

    Article  CAS  Google Scholar 

  21. Traitel T, Cohen Y, Kost J (2000) Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions. Biomaterials 21(16):1679–1687

    Article  CAS  Google Scholar 

  22. Tomer Gold (2001) Drug controlled release device based on enzymic degradation of a polymer matrix and diffusion: analytical models. M.Sc. Thesis, Technion—Israel Institute of Technology, Haifa

    Google Scholar 

  23. Singh S (2010) Nanomedicine-nanoscale drugs and delivery systems. J Nanosci Nanotechnol 10(12):7906–7918

    Article  CAS  Google Scholar 

  24. Gaffney J, Matou-Nasri S, Grau-Olivares M, Slevin M (2009) Therapeutic applications of hyaluronan. Mol Biosyst 6(3):437–443

    Article  Google Scholar 

  25. Singh M, Briones M, O’Hagan DT (2001) A novel bioadhesive intranasal delivery system for inactivated influenza vaccines. J Control Release 70(3):267–276

    Article  CAS  Google Scholar 

  26. Challa R, Ahuja A, Ali J, Khar RK (2005) Cyclodextrins in drug delivery: an updated review. AAPS Pharm Sci Tech 6(2):E329–E357

    Article  Google Scholar 

  27. Heise T, Brugger A, Cook C, Eckers U, Hutchcraft A, Nosek L, Rave K, Troeger J, Valaitis P, White S, Heinemann L (2009) PROMAXX inhaled insulin: safe and efficacious administration with a commercially available dry powder inhaler. Diabetes Obes Metab 11(5):455–459

    Article  CAS  Google Scholar 

  28. Lim ST, Martin GP, Berry DJ, Brown MB (2000) Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release 66(2–3):281–292

    Article  CAS  Google Scholar 

  29. Maham A, Tang Z, Wu H, Wang J, Lin Y (2009) Protein-based nanomedicine platforms for drug delivery. Small 5(15):1706–1721

    Article  CAS  Google Scholar 

  30. Sehgal PK, Srinivasan A (2009) Collagen-coated microparticles in drug delivery. Expert Opin Drug Deliv 6(7):687–695

    Article  CAS  Google Scholar 

  31. Basu SK, Kavitha K, Rupeshkumar M (2009) Evaluation of Ketorolac romethamine Microspheres by Chitosan/Gelatin B Complex Coacervation. Sci Pharm 78(1):79–92

    Article  Google Scholar 

  32. Golumbek PT, Azhari R, Jaffee EM, Levitsky HI, Lazenby A, Leong K, Pardoll DM (1993) Controlled release, biodegradable cytokine depots: a new approach in cancer vaccine design. Cancer Res 53(24):5841–5844

    CAS  Google Scholar 

  33. Hanes J, Sills A, Zhao Z, Suh KW, Tyler B, DiMeco F, Brat DJ, Choti MA, Leong KW, Pardoll DM, Brem H (2001) Controlled local delivery of interleukin-2 by biodegradable polymers protects animals from experimental brain tumors and liver tumors. Pharm Res 18(7):899–906

    Article  CAS  Google Scholar 

  34. Bourke SL, Kohn J (2003) Polymers derived from the amino acid L-tyrosine: polycarbonates, polyarylates and copolymers with poly(ethylene glycol). Adv Drug Deliv Rev 55(4):447–466

    Article  CAS  Google Scholar 

  35. Duncan R, Ringsdorf H, Satchi-Fainaro R (2006) Polymer therapeutics–polymers as drugs, drug and protein conjugates and gene delivery systems: past, present and future opportunities. J Drug Target 14(6):337–341

    Article  CAS  Google Scholar 

  36. Yang J, Jacobsen MT, Pan H, Kopecek J (2010) Synthesis and characterization of enzymatically degradable PEG-based peptide-containing hydrogels. Macromol Biosci 10(4):445–454

    Article  CAS  Google Scholar 

  37. Ohya Y, Takamido S, Nagahama K, Ouchi T, Katoono R, Yui N (2009) Polyrotaxane composed of poly-L-lactide and alpha-cyclodextrin exhibiting protease-triggered hydrolysis. Biomacromolecules 10(8):2261–2267

    Article  CAS  Google Scholar 

  38. Barbato F, La Rotonda MI, Maglio G, Palumbo R, Quaglia F (2001) Biodegradable microspheres of novel segmented poly(ether-ester-amide)s based on poly(epsilon-caprolactone) for the delivery of bioactive compounds. Biomaterials 22(11):1371–1378

    Article  CAS  Google Scholar 

  39. Giammona G, Pitarresi G, Cavallaro G, Buscemi S, Saiano F (1999) New biodegradable hydrogels based on a photocrosslinkable modified polyaspartamide: synthesis and characterization. Biochim Biophys Acta 1428(1):29–38

    Article  CAS  Google Scholar 

  40. Yoshida M, Asano M, Kumakura M, Katakai R, Mashimo T, Yuasa H, Imai K, Yamanaka H (1990) Sequential polydepsipeptides as biodegradable carriers for drug delivery systems. J Biomed Mater Res 24(9):1173–1184

    Article  CAS  Google Scholar 

  41. Moon HJ, Choi BG, Park MH, Joo MK, Jeong B (2011) Enzymatically degradable thermogelling poly(alanine-co-leucine)-poloxamer-poly(alanine-co-leucine). Biomacromolecules 12(4):1234–1242

    Article  CAS  Google Scholar 

  42. Tokatlian T, Shrum CT, Kadoya WM, Segura T (2010) Protease degradable tethers for controlled and cell-mediated release of nanoparticles in 2- and 3-dimensions. Biomaterials 31(31):8072–8080

    Article  CAS  Google Scholar 

  43. Yaacobi Y, Sideman S, Lotan N (1985) A mechanistic model for the enzymic degradation of synthetic biopolymers. Life Support Syst 3(4):313–326

    CAS  Google Scholar 

  44. Gopferich A, Langer R (1995) Modeling monomer release from bioerodible polymers. J control Release 33:55–69

    Article  Google Scholar 

  45. Lemaire V, Belair J, Hildgen P (2003) Structural modeling of drug release from biodegradable porous matrices based on combined diffusion/erosion process. Int J Pharm 258:95–107

    Article  CAS  Google Scholar 

  46. Arifin DY, Lee LY, Wang CH (2006) Mathematical modeling and simulation of drug release from microspheres: implications to drug delivery systems. Adv Drug Delivery Rev 58:1274–1325

    Article  CAS  Google Scholar 

  47. Lao LL, Venkatraman SS, Peppas NA (2008) Modeling of drug release from biodegradable polymer blends. Eur J Pharm Biopharm 70:796–803

    Article  CAS  Google Scholar 

  48. Yu R, Chen H, Chen T, Zhou X (2008) Modeling and simulation of drug release from multi-layer biodegradable microstructure in three dimensions. Simul Model Prac Theory 16:15–25

    Article  Google Scholar 

  49. Siepmann J, Siepmann F (2008) Mathematical modeling of drug delivery. Int J Pharm 364:328–343

    Article  CAS  Google Scholar 

  50. Barba AA, d’Amore M, Chirico S, Lamberti G, Titomanlio G (2009) A general code to predict the drug release kinetics from different shaped matrices. Eur J Pharm Sci 36:359–368

    Article  CAS  Google Scholar 

  51. Soares J, Zunino P (2010) A mixture model for water uptake, degradation, erosion and drug release from polydisperse polymeric networks. Biomaterials 31:3032–3042

    Article  CAS  Google Scholar 

  52. Brandl F, Kastner F, Gschwind RM, Blunk T, Tebmar J, Gopferich A (2010) Hydrogel-based drug delivery systems: comparison of drug diffusivity and release kinetics. J Control Release 142:221–228

    Article  CAS  Google Scholar 

  53. Azhari R, Sideman S, Lotan N (1991) A generalized model for enzymic depolymerization processes: Part I—Reaction pathways and kinetics. Polym Degrad Stab 33(1):35–52

    Article  CAS  Google Scholar 

  54. Azhari R, Lotan N (1991) Enzymic hydrolysis of biopolymers via single-scission attack pathways: a unified kinetic model. J Mater Sci Mater Med 2:9–18

    Article  CAS  Google Scholar 

  55. Azhari R, Lotan N (1991) Enzymic depolymerization processes: reaction pathways as a basis for a new classification and nomenclature. J Mater Sci Lett 10:243–245

    Article  CAS  Google Scholar 

  56. Tzafriri AR, Bercovier M, Parnas H (2002) Reaction diffusion model of the enzymatic erosion of insoluble fibrillar matrices. Biophys J 83(2):776–793

    Article  CAS  Google Scholar 

  57. Tayal A, Khan SA (2000) Degradation of a water-soluble polymer: molecular weight changes and chain scission characteristics. Macromolecules 33(26):9488–9493

    Article  CAS  Google Scholar 

  58. Watanabe M, Kawai F (2006) Mathematical modelling and computational analysis of enzymatic degradation of xenobiotic polymers. Appl Math Model 30(12):1497–1514

    Article  Google Scholar 

  59. Klemchuka PP (1990) Degradable plastics: a critical review. Polym Degrad Stab 27(2):183–202

    Article  Google Scholar 

  60. Maeda H, Ymagata Y, Abe K, Hasegawa F, Machida M, Ishioka R, Gomi K, Nakajima T (2005) Purification and characterization of a biodegradable plastic-degrading enzyme from Aspergillus oryzae. Appl Microbiol Biotechnol 67:778–788

    Article  CAS  Google Scholar 

  61. Maron MJ (1982) Numerical analysis, a practical approach, 2nd edn. MacMillan publishing, New York

    Google Scholar 

  62. Crank J (1975) The mathematics of diffusion, 2nd edn. Clarendon Press, Oxford

    Google Scholar 

  63. Smith GD (1986) Numerical solution of partial differential equations: finite difference method, 3rd edn. Oxford University Press, Oxford

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Biomedical Engineering, Technion—Israel Institute of Technology, Haifa, Israel

    Tomer Gold & Noah Lotan

  2. Department of Biotechnology Engineering, ORT Braude College, Karmiel, Israel

    Rosa Azhari

Authors
  1. Tomer Gold
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rosa Azhari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Noah Lotan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Noah Lotan .

Editor information

Editors and Affiliations

  1. Fac. Engineering, School of Mechanical Engineering, Tel Aviv University, Ramat Aviv, Tel-Aviv, 69978, Israel

    Noam Eliaz

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media New York

About this chapter

Cite this chapter

Gold, T., Azhari, R., Lotan, N. (2012). Enzyme-Promoted Degradation of Polymeric Matrices for Controlled Drug Delivery: Analytical Model and Numerical Simulations. In: Eliaz, N. (eds) Degradation of Implant Materials. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3942-4_8

Download citation

Publish with us

Policies and ethics

Search

Navigation