Pharmaceutical Research

, Volume 8, Issue 6, pp 713–720

Controlled Delivery Systems for Proteins Based on Poly(Lactic/Glycolic Acid) Microspheres


  • Smadar Cohen
    • Department of Chemical EngineeringMIT
  • Toshio Yoshioka
    • Department of Chemical EngineeringMIT
  • Melissa Lucarelli
    • Department of Chemical EngineeringMIT
  • Lena H. Hwang
    • Department of Chemical EngineeringMIT
  • Robert Langer
    • Department of Chemical EngineeringMIT

DOI: 10.1023/A:1015841715384

Cite this article as:
Cohen, S., Yoshioka, T., Lucarelli, M. et al. Pharm Res (1991) 8: 713. doi:10.1023/A:1015841715384


This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55–95 µm and encapsulated more than 90% of the protein. The preparation method was gentle and maintained enzyme activity and protein solubility. Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss. When not placed inside PLGA microspheres, (fluorescein isothiocyanate)-labeled horseradish peroxidase lost 80% of its activity in solution at 37°C in a few days, whereas inside the PLGA microspheres it retained more than 55% of its activity after 21 days of incubation at 37°C. In vitro release studies revealed that different release profiles (i.e., near-constant or biphasic) and release rates can be achieved by simply modifying factors in the preparation procedure such as mixing rate and volume of inner water and organic phases. Degradation studies by scanning electron microscopy and gel-permeation chromatography suggested that the mechanism responsible for protein release is mainly through matrix erosion.

protein delivery systemcontrolled releaseenzyme stabilitypoly(lactic/glycolic acid)biodegradable microspheres

Copyright information

© Plenum Publishing Corporation 1991