PLGA-MICROSPHERES AS A RELEASE-SYSTEM FOR

European Cells and Materials Vol. 14. Suppl. 1, 2007 (page 57)
ISSN 1473-2262
PLGA-MICROSPHERES AS A RELEASE-SYSTEM FOR SIGNALLING
MOLECULES IN TISSUE ENGINEERING – FIRST RESULTS OF
PROSTAGLANDIN E2 RELEASE
C. Brochhausen1, R. Zehbe2, B. Watzer3, S. Halstenberg1, H. Schubert2, C.J. Kirkpatrick1
1
REPAIRlab, Institute of Pathology, Johannes Gutenberg-University, Mainz, D
2
Institute of Materials Science and Technology, Technical University, Berlin, D
³Mother-Child Medical Center, Department of Pediatric Science, Philipps-University,
Marburg, D
INTRODUCTION: In Tissue Engineering
solutions signaling molecules and growth
factors have become very attractive.
Prostaglandin E2 (PGE2) is involved in
physiological homeostasis and numerous
pathophysiological conditions, such as stress
response and inflammation. Furthermore, it has
already been demonstrated that prostaglandins
have stimulating effects not only on
angiogenesis in situ and in vitro but also
fracture healing in situ. 1,2 Thus, PGE2
represents an interesting target molecule as a
therapeutic agent to promote angiogenesis and
to support healing of major bone defects in the
scope of tissue engineering strategies. However,
the half life of PGE2 is very low, with a value of
approximately 10 minutes under physiological
conditions. We tested if the release of
prostaglandin E2 could be prolonged by its
integration in a degradable poly (D,L-lactideco-glycolide) (PLGA) -based microsphere.
METHODS: PGE2-modified microspheres
were produced by dissolving PLGA (85:15 lactide-glycolide ratio) in CHCl3 and adding a
solution of PGE2 in a fluorinated alcohol. This
solution was added drop wise with to a stirring
0.5 % polyvinyl alcohol as emulsifier. The
solution was left stirring overnight to allow
complete evaporation of the used solvents.
Twelve identical microsphere batches were
produced; with 1.0 ml of serum-free medium
added to each. The supernatant was removed at
different time points (0, 0.5, 1, 2, 4, 6, 13, 24,
48, 72, 154 h). PGE2 release rates were
measured by gas chromatography – mass
spectrometry (GC-MS).
RESULTS: A steady release of PGE2 could be
observed with a maximum at 24 hours followed
by a discrete decrease within the following 5
days (Fig. 1). Thus, PGE2 could be integrated
into PLGA-based microspheres. Furthermore,
the microspheres allowed a steady release of
PGE2 over 24 hours. The exact kinetics and the
mechanisms of release (diffusion vs.
biochemical changes of the microspheres) need
further investigations. Furthermore, the cause
for the decrease of PGE2 still has to be clarified.
Fig. 1: PGE2 (ng/ml) levels in the supernatants
after 0, 0.5, 1, 2, 4, 6, 13, 24, 48, 72 and 154
hours measured by GC/MS
DISCUSSION & CONCLUSIONS: PGE2 can
be integrated into PLGA-based microspheres.
PLGA release PGE2 in its unchanged
biologically active form with one maximum at
24 hours. Since PGE2 has a limited half life of
10 minutes under physiological conditions the
encapsulation in microspheres could allow a
prolonged effect. As well as the structural
integrity, the functionality of released PGE2 has
to be tested in further analyses.
In conclusion, our first results of the
encapsulation and release of PGE2 from PLGAbased microspheres open up interesting aspects
for the use of microspheres as release system
for signaling molecules in various tissue
engineering strategies.
REFERENCES: 1 A.M. Flanagan, T.J.
Chambers (1992) Endocrinology 130:443-48.
2
M. Weinreb, S.J. Rutledge, G.A. Rodan
(1997) Bone 20:347-58.