Dermatan sulfate as a stabilizer for protein stability in poly(lactide-co-glycolide) depot

Wooram Park, Kun Na

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16 Scopus citations

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.

Original languageEnglish
Pages (from-to)668-674
Number of pages7
JournalBiotechnology and Bioprocess Engineering
Volume14
Issue number5
DOIs
StatePublished - Oct 2009

Bibliographical note

Funding Information:
Acknowledgements This research was financially supported by the Ministry of Knowledge Economy (MKE) and the Korea Industrial Technology Foundation (KOTEF) through the Human Resource Training Project for Strategic Technology.

Keywords

  • Dermatan sulfate
  • PLGA depot
  • Polyelectrolyte complex
  • Protein stability
  • Water-in-oil-in-water (W/O/W )

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