Skip to main content
SpringerLink
Log in

Designing drug-loaded multi-layered polymeric microparticles

  • Published:
Journal of Materials Science: Materials in Medicine Aims and scope Submit manuscript

Abstract

This work reports how novel multi-layered (from double-layered to quadruple-layered) microparticles comprising immiscible polymers can be fabricated through a simple, economical, reliable and versatile one-step solvent evaporation method. These multi-layered microparticles would be excellent candidates to overcome problems inherent in single-layered microparticles for drug delivery. Particle morphologies, layer configurations, and drug distribution were determined by scanning electron microscopy and Raman mapping. Key process parameters achieving the formation of the multi-layered structure were identified. Encapsulation of multiple drugs and layer localization of these drugs within these multi-layered microparticles have also shown to be possible, which were driven by drug-polymer affinity. This one-step fabrication technique can therefore be used for tailoring particle designs, thus facilitating the development of multiparticulate drug delivery devices.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Freiberg S, Zhu X. Polymer microspheres for controlled drug release. Int J Pharm. 2004;282(1–2):1–18.

    Article  CAS  Google Scholar 

  2. Brannon-Peppas L. Recent advances on the use of biodegradable micropraticles and nanoparticles in controlled drug-delivery. Int J Pharm. 1995;116(1):1–9.

    Article  CAS  Google Scholar 

  3. Freitas S, Merkle HP, Gander B. Microencapsulation by solvent extraction/evaporation: reviewing the state of the art of microsphere preparation process technology. J Control Release. 2005;102(2):313–32.

    Article  CAS  Google Scholar 

  4. Jalil R, Nixon JR. Microencapsulation using poly (l-lactic acid) IV: release properties of microcapsules containing phenobarbitone. J Microencapsul. 1990;7(1):53–66.

    Article  CAS  Google Scholar 

  5. Pekarek KJ, Jacob JS, Mathiowitz E. Double-walled polymer microspheres for controlled drug-release. Nature. 1994;367(6460):258–60.

    Article  CAS  Google Scholar 

  6. Sanchez A, Gupta RK, Alonso MJ, Siber GR, Langer R. Pulsed controlled-release system for potential use in vaccine delivery. J Pharm Sci. 1996;85(6):547–52.

    Article  CAS  Google Scholar 

  7. Rodriguez M, Vila-Jato JL, Torres D. Design of a new multiparticulate system for potential site-specific and controlled drug delivery to the colonic region. J Control Release. 1998;55(1):67–77.

    Article  CAS  Google Scholar 

  8. Lee TH, Wang JJ, Wang CH. Double-walled microspheres for the sustained release of a highly water soluble drug: characterization and irradiation studies. J Control Release. 2002;83(3):437–52.

    Article  CAS  Google Scholar 

  9. Shi M, Yang YY, Chaw CS, Goh SH, Moochhala SM, Ng S, et al. Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties. J Control Release. 2003;89(2):167–77.

    Article  CAS  Google Scholar 

  10. Rahman NA, Mathiowitz E. Localization of bovine serum albumin in double-walled microspheres. J Control Release. 2004;94(1):163–75.

    Article  CAS  Google Scholar 

  11. Berkland C, Cox A, Kim K, Pack DW. Three-month, zero-order piroxicam release from monodispersed double-walled microspheres of controlled shell thickness. J Biomed Mater Res. 2004;70A(4):576–84.

    Article  CAS  Google Scholar 

  12. Pekarek KJ, Dyrud MJ, Ferrer K, Jong YS, Mathiowitz E. In vitro and in vivo degradation of double-walled polymer microspheres. J Control Release. 1996;40(3):169–78.

    Article  CAS  Google Scholar 

  13. Lee WL, Loei C, Widjaja E, Loo SCJ. Altering the drug release profiles of double-layered ternary-phase microparticles. J Control Release. 2011;151:229–38.

    Article  CAS  Google Scholar 

  14. Gopferich A, Alonso MJ, Langer R. Development and characterization of microencapsulated microspheres. Pharm Res. 1994;11(11):1568–74.

    Article  CAS  Google Scholar 

  15. Watano S, Nakamura H, Hamada K, Wakamatsu Y, Tanabe Y, Dave RN, et al. Fine particle coating by a novel rotating fluidized bed coater. Powder Technol. 2004;141(3):172–6.

    Article  CAS  Google Scholar 

  16. Wang FJ, Wang CH. Sustained release of etanidazole from spray dried microspheres prepared by non-halogenated solvents. J Control Release. 2002;81(3):263–80.

    Article  CAS  Google Scholar 

  17. Lee HK, Park JH, Kwon KC. Double-walled microparticles for single shot vaccine. J Control Release. 1997;44(2–3):283–93.

    CAS  Google Scholar 

  18. Pollauf EJ, Kim KK, Pack DW. Small-molecule release from poly (d,l-lactide)/poly (d,l-lactide-co-glycolide) composite microparticles. J Pharm Sci. 2005;94(9):2013–22.

    Article  CAS  Google Scholar 

  19. Berkland C, Pollauf E, Pack DW, Kim K. Uniform double-walled polymer microspheres of controllable shell thickness. J Control Release. 2004;96(1):101–11.

    Article  CAS  Google Scholar 

  20. Lee WL, Foo WL, Widjaja E, Loo SCJ. Manipulation of process parameters to achieve different ternary-phase microparticle configurations. Acta Biomater. 2010;6:1342–52.

    Article  CAS  Google Scholar 

  21. Mathiowitz E, Langer RS. Preparation of multiwall polymeric microcapsules. US Patent No. 4861627; 1989.

  22. Pekarek KJ, Jacob JS, Mathiowitz E. One-step preparation of double-walled microspheres. Adv Mater. 1994;6(9):684–7.

    Article  CAS  Google Scholar 

  23. Tan EC, Lin RY, Wang CH. Fabrication of double-walled microspheres for the sustained release of doxorubicin. J Colloid Interface Sci. 2005;291(1):135–43.

    Article  CAS  Google Scholar 

  24. Leach K, Noh K, Mathiowitz E. Effect of manufacturing conditions on the formation of double-walled polymer microspheres. J Microencapsul. 1999;16(2):153–67.

    Article  CAS  Google Scholar 

  25. Mathiowitz E, Jacob JS, Chickering Iii DE, Pekarek KJ. Preparation of multiwall polymeric microcapsules from hydrophilic polymers. US Patent No. 6511749; 2003.

  26. Pollauf EJ, Pack DW. Use of thermodynamic parameters for design of double-walled microsphere fabrication methods. Biomaterials. 2006;27(14):2898–906.

    Article  CAS  Google Scholar 

  27. Loxley A, Vincent B. Preparation of poly(methylmethacrylate) microcapsules with liquid cores. J Colloid Interface Sci. 1998;208(1):49–62.

    Article  CAS  Google Scholar 

  28. Widjaja E, Lee WL, Loo SCJ. Application of Raman microscopy to biodegradable double-walled microspheres. Anal Chem. 2010;82:1277–82.

    Article  CAS  Google Scholar 

  29. Widjaja E, Li CZ, Chew W, Garland M. A general and robust algorithm for pure component spectral recovery. Band target entropy minimization. Anal Chem. 2003;75:4499–507.

    Article  CAS  Google Scholar 

  30. O’Donnell PB, McGinity JW. Preparation of microspheres by the solvent evaporation technique. Adv Drug Deliv Rev. 1997;28(1):25–42.

    Article  Google Scholar 

  31. Mao SR, Shi Y, Li L, Xu J, Schaper A, Kissel T. Effects of process and formulation parameters on characteristics and internal morphology of poly(d,l-lactide-co-glycolide) microspheres formed by the solvent evaporation method. Eur J Pharm Biopharm. 2008;68(2):214–23.

    Article  CAS  Google Scholar 

  32. Matsumoto A, Matsukawa Y, Suzuki T, Yoshino H, Kobayashi M. The polymer–alloys method as a new preparation method of biodegradable microspheres: principle and application to cisplatin-loaded microspheres. J Control Release. 1997;48(1):19–27.

    Article  CAS  Google Scholar 

  33. Wang Y, Guo BH, Wan X, Xu J, Wang X, Zhang YP. Janus-like polymer particles prepared via internal phase separation from emulsified polymer/oil droplets. Polymer. 2009;50(14):3361–9.

    Article  CAS  Google Scholar 

  34. Krevelen DW, Hoftyzer PJ. Properties of polymers their estimation and correlation with chemical structure. Amsterdam: Elsevier; 1976.

    Google Scholar 

Download references

Acknowledgements

This work was supported by National Medical Research Council (NMRC) Exploratory Development Grant (NMRC/EDG/0062/2009).

Author information

Authors and Affiliations

  1. School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore

    Wei Li Lee & Say Chye Joachim Loo

  2. Process Science and Modeling, Institute of Chemical and Engineering Sciences, 1 Pesek Road, Jurong Island, Singapore, 627833, Singapore

    Effendi Widjaja

Authors
  1. Wei Li Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Effendi Widjaja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Say Chye Joachim Loo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Say Chye Joachim Loo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, W.L., Widjaja, E. & Loo, S.C.J. Designing drug-loaded multi-layered polymeric microparticles. J Mater Sci: Mater Med 23, 81–88 (2012). https://doi.org/10.1007/s10856-011-4508-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10856-011-4508-z

Keywords

Search

Navigation