Effects of hydrophilic cyclodextrins on aggregation of recombinant human growth hormone
| Autor: | Shinichiro Tajiri, Hidetoshi Arima, Kaneto Uekama, Fumitoshi Hirayama, Sumitra Tavornvipas |
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| Rok vydání: | 2005 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Cyclodextrins Aqueous solution Molecular mass Chemistry Globular protein Human Growth Hormone Organic Chemistry Pharmaceutical Science Peptide Protein tertiary structure Recombinant Proteins Hydrophobic effect Biophysics Molecular Medicine Organic chemistry Humans Pharmacology (medical) Denaturation (biochemistry) Deamidation Biotechnology |
| Zdroj: | Pharmaceutical research. 21(12) |
| ISSN: | 0724-8741 |
| Popis: | To evaluate the effect of hydrophilic cyclodextrins (CyDs) on the aggregation induced by different stresses and on the oxidation and deamidation of recombinant human growth hormone (rhGH).The aggregation of rhGH was induced by three denaturing techniques including chemical (4.5 M guanidine hydrochloride), thermal (differential scanning calorimetry), and interfacial denaturation (vortex agitation). The aggregates were characterized and quantified by UV spectrophotometry and size exclusion chromatography. The effects of hydrophilic CyDs on deamidation and oxidation rates of rhGH were studied by HPLC method.In both thermally and chemically induced aggregations, branched beta-CyDs significantly inhibited the aggregation of rhGH compared with the other alpha- and gamma-CyDs. This can explain that the beta-CyD cavity with branched sugar moieties may be relatively preferable in preventing the aggregation of rhGH. In contrast, 2-hydroxypropyl beta-CyD with surface activity was found to be effective in reducing the aggregation induced by interfacial denaturation compared with those of branched beta-CyDs. On the other hand, these hydrophilic CyDs showed no noticeable inhibitory effect on the oxidation and deamidation rates of rhGH. The results suggested that CyDs interact preferably with exposed hydrophobic side chains rather than aliphatic side chains of rhGH, resulting in the inhibition of aggregation but not the oxidation and deamidation rates.The different inhibitory effect of CyDs is dependent not only on the structure and property of CyD itself but also the nature of the denaturing stimulus. The current results suggested that hydrophilic beta-CyDs can effectively inhibit the aggregation of rhGH. Thus, hydrophilic beta-CyDs may be potentially useful excipients for parenteral preparation of rhGH. |
| Databáze: | OpenAIRE |
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