Pharmaceutical Research

, Volume 31, Issue 11, pp 2940–2951 | Cite as

Modulating Protein Release Profiles by Incorporating Hyaluronic Acid into PLGA Microparticles Via a Spray Dryer Equipped with a 3-Fluid Nozzle

  • Feng Wan
  • Morten Jonas Maltesen
  • Sune Klint Andersen
  • Simon Bjerregaard
  • Stefania G. Baldursdottir
  • Camilla Foged
  • Jukka Rantanen
  • Mingshi Yang
Research Paper



The purpose of this study was to modulate the release profiles of the model protein drug from spray dried poly(DL-lactic-co-glycolic acid) (PLGA) microparticles by incorporating hyaluronic acid (HA) in the formulation.


Bovine serum albumin (BSA)-loaded PLGA microparticles with or without HA were prepared using a spray dryer equipped with a 3-fluid nozzle. The effects of HA on the surface tension and the rheological behavior of the inner feed solution were investigated. The physicochemical properties of the resulting microparticles were characterized using scanning electron microscopy (SEM), laser diffraction (LD), confocal laser scanning microscopy (CLSM) and X-ray photoelectron spectroscopy (XPS). Circular dischoism (CD) was used to characterize conformational integrity of BSA released from the microparticles.


Spherical microparticles with D50 of 5–10 μm were obtained. Addition of HA in inner feed solutions increased the feed viscosity, but with no influence on the surface tension. All inner feed solutions showed non-Newtonian shear thinning behavior and the rheological properties were not time dependent. The CLSM and XPS analyses suggested a core-shell like structure of the microparticles when HA was incorporated. The release profiles of BSA were extended and the initial burst releases were suppressed with an increase in HA in the microparticle formulations. In addition, HA seemed to protect BSA from degradation upon the spray-drying process.


The present work demonstrates the potential of HA to modulate protein release profile from PLGA microparticle formulations produced via spray drying using 3-fluid nozzle.


controlled release hyaluronic acid microencapsulation PLGA microparticles protein spray drying 



This work was funded by The Danish Council for Technology and Innovation via the Innovation Consortium NanoMorph (952320/2009), The Drug Research Academy and The Danish Agency for Science, Technology and Innovation. The authors would also like to thank Kenneth Brian Haugshøj (Danish Technological Institute) and Pia Wahlberg (Danish Technological Institute) for technical assistance with XPS analysis, and Thomas Hartig Braunstein (Core Facility for Integrated Microscopy, University of Copenhagen) and Laure Plantard (Core Facility for Integrated Microscopy, University of Copenhagen) for technical assistance with CLSM analysis.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Feng Wan
    • 1
  • Morten Jonas Maltesen
    • 2
  • Sune Klint Andersen
    • 3
  • Simon Bjerregaard
    • 3
  • Stefania G. Baldursdottir
    • 1
  • Camilla Foged
    • 1
  • Jukka Rantanen
    • 1
  • Mingshi Yang
    • 1
  1. 1.Department of Pharmacy, Faculty of Health and Medical SciencesUniversity of CopenhagenCopenhagen ØDenmark
  2. 2.Biopharma Application Development, Novozymes A/SBagsvaerdDenmark
  3. 3.Preformulation and Delivery/Oral Protein Delivery, Diabetes Research Unit, Novo Nordisk A/SMåløvDenmark

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