Dermatan sulfate as a stabilizer for protein stability in poly(lactide-co-glycolide) depot |
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Authors: | Wooram Park Kun Na |
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Institution: | (1) School of Pharmacy, Shanghai Jiaotong University, Shanghai, 200240, China; |
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Abstract: | Dermatan sulfate (DS), a glycosaminoglycan family, was investigated as a additive to enhance the stability of therapeutic
protein with low p/ value loaded in poly(lactide-co-glycolide) (PLGA) microspheres prepared by water-in-oil-in-water (W1/O/W2) method. DS maintains negative charge below pH 3.0 because of its sulfate groups, while most anionic polymer with carboxyl
groups becomes neutral charge at that pH. Thus, at pH 3.0 DS can form a polyelectrolyte complex with a protein with lower
p/ such as exendin-4, insulin, and human growth hormone. In order to complex with DS, bovine serum albumin (BSA) was employed
as a model protein, which has low p/value (p/= 4.8). The complex prepared at pH 3.0 showed a nano-size in the range of 100∼200
nm with a mono distribution. During the preparation of PLGA depot, DS concentration in water phase increases with decreasing
the formation of non-covalent BSA aggregates and enhancing BSA loading efficiency. It means that DS/BSA complex system enabled
to keep a stability of BSA at the water/organic interface. In an in vitro BSA release test, PLGA depot with DS exhibited a lower initial burst kinetic than only PLGA depot and continuous BSA release
in almost 100% for 23 days. From the results, it was concluded that DS as an additive in PLGA depot, has a potential for the
long-term delivery of therapeutic proteins with lower p/ value. |
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