Abstract
Nanotechnology has been applied to the development of more effective and compatible drug delivery systems for therapeutic proteins. Human growth hormone (hGH) was fused with a hybrid Fc fragment containing partial Fc domains of human IgD and IgG4 to produce a long-acting fusion protein. The fusion protein, hGH-hyFc, resulted in the increase of the hydrodynamic diameter (ca. 11 nm) compared with the diameter (ca. 5 nm) of the recombinant hGH. A diblock copolymer membrane with nanopores (average diameter of 14.3 nm) exhibited a constant release rate of hGH-hyFc. The hGH-hyFc protein released in a controlled manner for one month was found to trigger the phosphorylation of Janus kinase 2 (JAK2) in human B lymphocyte and to exhibit an almost identical circular dichroism spectrum to that of the original hGH-hyFc, suggesting that the released fusion protein should maintain the functional and structural integrity of hGH. Thus, the nanoporous release device could be a potential delivery system for the long-term controlled release of therapeutic proteins fused with the hybrid Fc fragment.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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B-Lymphocytes / cytology
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B-Lymphocytes / enzymology
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Cell Line
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Delayed-Action Preparations / chemical synthesis
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Delayed-Action Preparations / chemistry
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Delayed-Action Preparations / pharmacokinetics
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Delayed-Action Preparations / pharmacology
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Human Growth Hormone* / biosynthesis
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Human Growth Hormone* / genetics
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Human Growth Hormone* / pharmacokinetics
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Human Growth Hormone* / pharmacology
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Humans
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Immunoglobulin D* / biosynthesis
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Immunoglobulin D* / genetics
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Immunoglobulin D* / pharmacology
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Immunoglobulin Fc Fragments* / biosynthesis
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Immunoglobulin Fc Fragments* / genetics
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Immunoglobulin Fc Fragments* / pharmacology
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Immunoglobulin G* / biosynthesis
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Immunoglobulin G* / genetics
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Immunoglobulin G* / pharmacology
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Janus Kinase 2 / metabolism
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Membranes, Artificial*
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Phosphorylation / drug effects
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Porosity
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Protein Stability
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Recombinant Fusion Proteins* / biosynthesis
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Recombinant Fusion Proteins* / genetics
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Recombinant Fusion Proteins* / pharmacokinetics
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Recombinant Fusion Proteins* / pharmacology
Substances
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Delayed-Action Preparations
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Immunoglobulin D
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Immunoglobulin Fc Fragments
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Immunoglobulin G
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Membranes, Artificial
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Recombinant Fusion Proteins
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Human Growth Hormone
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JAK2 protein, human
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Janus Kinase 2