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.
| Original language | English |
|---|---|
| Pages (from-to) | 613-622 |
| Number of pages | 10 |
| Journal | Journal of Pharmaceutical Sciences |
| Volume | 105 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2016 Feb 1 |
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Keywords
- biological activity
- HA microparticle
- recombinant human growth hormone
- spray-drying
- structural integrity
- sustained release formulation
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying. / Kim, Sun J.; Kim, Chan Wha.
In: Journal of Pharmaceutical Sciences, Vol. 105, No. 2, 01.02.2016, p. 613-622.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Development and Characterization of Sodium Hyaluronate Microparticle-Based Sustained Release Formulation of Recombinant Human Growth Hormone Prepared by Spray-Drying
AU - Kim, Sun J.
AU - Kim, Chan Wha
PY - 2016/2/1
Y1 - 2016/2/1
N2 - 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.
AB - 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.
KW - biological activity
KW - HA microparticle
KW - recombinant human growth hormone
KW - spray-drying
KW - structural integrity
KW - sustained release formulation
UR - http://www.scopus.com/inward/record.url?scp=84964417421&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84964417421&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2015.11.046
DO - 10.1016/j.xphs.2015.11.046
M3 - Article
C2 - 26869423
AN - SCOPUS:84964417421
VL - 105
SP - 613
EP - 622
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 2
ER -