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KMID : 1094720090140050668
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Biotechnology and Bioprocess Engineering
2009 Volume.14 No. 5 p.668 ~ p.674
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Dermatan Sulfate as a Stabilizer for Protein Stability in Poly(lactide-co-glycolide) Depot
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Park Woo-Ram
Na Kun
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Abstract
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Dermatan sulfate (DS), a glycosaminoglycan family, was investigated as a additive to enhance the stability of therapeutic protein with low pI 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 pI 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 pI value (pI = 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 pI value.
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KEYWORD
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dermatan sulfate, PLGA depot, water-in-oil-in-water (W1/O/W2), protein stability, polyelectrolyte complex
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