Pharmaceutical Research

, Volume 23, Issue 4, pp 782–789 | Cite as

Osmotic-Driven Release Kinetics of Bioactive Therapeutic Proteins from a Biodegradable Elastomer are Linear, Constant, Similar, and Adjustable

Research Paper


The aim of the study is to determine whether a biodegradable elastomeric device that uses an osmotic pressure delivery mechanism can release different therapeutic proteins at a nearly constant rate in nanomolar concentrations with high bioactivity, given the same formulation conditions. Vascular endothelial growth factor (VEGF) and interleukin-2 (IL-2) were embedded in the device as sample therapeutic proteins, and their release and bioactivity were compared to that achieved previously with interferon-γ (IFN-γ).


A photo-cross-linkable biodegradable macromer consisting of acrylated star(ɛ-caprolactone-co-d,l-lactide) was prepared. VEGF, IL-2, and IFN-γ were co-lyophilized with serum albumin and trehalose at different ratios and were then embedded into the elastomer by photo-cross-linking the lyophilized particles in a macromer solution. The protein mass and the bioactivity in the release supernatant were measured by enzyme-linked immunosorbent and cell-based assays.


VEGF, IL-2, and IFN-γ were released at the same, nearly constant rate of 25.4 ng/day for over 18 days. Using the optimum elastomer formulation, the release profiles of the proteins were essentially identical, and their rates were linear and constant. Cell-based bioactivity assays showed that 70 and 88% of the released VEGF and IL-2, respectively, were bioactive. The rate of protein release can be adjusted by changing the trehalose loading concentration in the elastomer matrix without altering the linear nature of the protein release kinetics. The elastomeric device degraded in PBS buffer within 85 days.


The elastomer formulation shows promising potential as a sustained protein drug delivery vehicle for local delivery applications.


Vascular Endothelial Growth Factor Trehalose Therapeutic Protein Protein Release PLGA Microsphere 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



acrylated star copolymer






star copolymer


vascular endothelial growth factor



The authors thank Norma Turner, Dr. Stephen Pang, and Dr. Yat Tse of Queen's University for their assistance. This research was financially supported by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of Chemical EngineeringQueen's UniversityKingstonCanada

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