title: Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying.
abstract: The purpose of this study was to develop and characterize a sodium hyaluronate microparticle-based sustained release formulation of recombinant human growth hormone (SR-rhGH) prepared by spray-drying. Compared to freeze-drying, spray-dried SR-rhGH showed not only prolonged release profiles but also better particle property and injectability. The results of size-exclusion high-performance liquid chromatography showed that no aggregate was detected, and dimer was just about 2% and also did not increase with increase of inlet temperature up to 150 °C. Meanwhile, the results of reversed-phase high-performance liquid chromatography revealed that related proteins increased slightly from 4.6% at 100 °C to 6.3% at 150 °C. Thermal mapping test proved that product temperature did not become high to cause protein degradation during spray-drying because thermal energy was used for the evaporation of surface moisture of droplets. The structural characterization by peptide mapping, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and circular dichroism revealed that the primary, secondary, and tertiary structures of rhGH in SR-rhGH were highly comparable to those of reference somatropin materials. The biological characterization by rat weight gain and cell proliferation assays provided that bioactivity of SR-rhGH was equivalent to that of native hGH. These data establish that spray-dried SR-rhGH is highly stable by preserving intact rhGH and hyaluronate microparticle-based formulation by spray-drying can be an alternative delivery system for proteins.
authors: Department of Biotechnology, University of Korea, Seoul, South Korea; Biotech Group, LG Life Sciences Company, Daejeon, South Korea.
authors: Sun J
authors: SJ
authors: Kim
authors: Department of Biotechnology, University of Korea, Seoul, South Korea. Electronic address: cwkim@korea.ac.kr.
authors: Chan W
authors: CW
authors: Kim
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000378:metabolism; D003890:Desiccation / Q000379:methods*; D005260:Female; D019382:Human Growth Hormone / Q000138:chemical synthesis* / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000138:chemical synthesis* / Q000378:metabolism; D008863:Microspheres; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D006820:Hyaluronic Acid
keywords: HA microparticle; biological activity; recombinant human growth hormone; spray-drying; structural integrity; sustained release formulation