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In
vitro evaluation and intra-articular administration of
biodegradable microspheres containing naproxen sodium
S. BOZDAІ,
S. ÇALIŞ †*,
H. S. KAކ, M. T. ERCAN‡,
İ.
PEKSOY‡ and A. A. HINCAL†
† Department of
Pharmaceutical Technology, Faculty of Pharmacy;
‡ Department of Nuclear Medicine, Faculty of Medicine, Hacettepe
University, 06100
Ankara, Turkey
Summary
The dispersion of
non-steroidal antiinflammatory drugs (NSAIDs) into
biodegradable polymeric matrices have been accepted as a good approach for
obtaining a therapeutic effect in a predetermined period of time meanwhile
minimizing
the side effects of NSAIDs. In the present study, it was aimed to
prepare Naproxen Sodium (NS), (a NSAID) loaded microsphere formulation
using
natural Bovine Serum Albumin (BSA) and synthetic biodegradable
polymers such as polydactide-co-glycolic acid) (PLGA) (50:50 MW 34000 and
88 000 Da)
for intra-articular administration, and to study the retention of the
drug at the
site of injection in the knee joint. NS incorporated microspheres
were
evaluated 'in vitro for particle size (the mean particle size; for
BSA
microspheres,
10.0±0.3um, for PLGA microspheres, 9.0 ± 0.2 and
5.0±0.1um
for MW 34000 and 88 000 Da, respectively), yield value, drug
loading,
surface morphology and drug release. For in vivo studies,
monoarticular arthritis was induced in the left knee joints of rabbits by
using
ovalbumm and
Freund's Complete Adjuvant as antigen and adjuvant. A certain
time (4
days) is allowed for the formation of arthritis in the knee joints, then
the
NS loaded
microspheres were injected directly into the articular cavity. At
specific
time points, gamma scintigrams were obtained to determine the
residence
time of the microspheres in knee joints, in order to determine the
most
suitable formulation. This study indicated that PLGA, a synthetic
polymer, is
more promising than the natural type BSA microspheres for an
effective
cure of mono-articular arthritis in rabbits.
Key
words
Naproxen
sodium, poly(lactide-co-glycolic acid) PLGA, bovine
serum albumin, controlled release, experimental arthritis, scintigraphic
imaging.
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