AI Article Synopsis
- The research compares different PEGylated forms of recombinant human granulocyte colony stimulating factor (rhG-CSF) to find a more cost-effective and efficient treatment for neutropenia.
- The study found that a higher molecular weight PEGylated version (mono-PEG30-GCSF) offers longer half-life in circulation and improved drug bioavailability compared to its lower molecular weight counterpart (mono-PEG20-GCSF).
- The results suggest that mono-PEG30-GCSF can be administered at a lower dosage while maintaining the same therapeutic effects, potentially reducing treatment costs.
Article Abstract
Recombinant human granulocyte colony stimulating factor (rhG-CSF) and its PEGylated product "mono-PEG20-GCSF" have already been widely used for treatment of all kinds of neutropenia. However, the high required dosage of mono-PEG20-GCSF made it relatively expensive in clinical use. We postulated that an N-terminal site-specific PEGylated rhG-CSF with higher PEG Mw (PEG30 kDa) might be able to achieve longer circulation half-life while retaining its bioactivity, allowing the reduction of dosage for clinical use. rhG-CSF was PEGylated at the N-terminus by 5 kDa, 10 kDa, 20 kDa and 30 kDa methoxy-poly(ethylene glycol)-propionaldehyde (mPEG-ALD), and the four PEGylates were compared with respect to reaction, separation, characterization and also in vivo/in vitro activity, results showed that the mPEG-ALD of higher Mw demonstrated better N-terminal site-specific selectivity, separation purity and yield. The production cost and in vitro activity of mono-PEG30-GCSF and mono-PEG20-GCSF were almost the same, while mono-PEG30-GCSF showed longer in vivo circulation half-life and 60% higher drug bioavailability than mono-PEG20-GCSF. Consequently, mono-PEG30-GCSF shall be administered at a lower dosage than mono-PEG20-GCSF while retaining the same therapeutic efficacy.
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| http://dx.doi.org/10.1016/j.jbiotec.2009.05.012 | DOI Listing |
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