Reference - Detail
| RRC ID | 45378 |
|---|---|
| Author | Shiga Y, Oshima Y, Kojima Y, Sugimoto A, Tamaki N, Murata D, Takeuchi T, Sato A. |
| Title | Recombinant human lactoferrin-Fc fusion with an improved plasma half-life. |
| Journal | Eur J Pharm Sci |
| Abstract |
Lactoferrin (LF), an 80-kDa iron-binding glycoprotein found in mammalian exocrine secretions, has potential therapeutic efficacy due to its extensive health-promoting effects. However, LF is rapidly cleared from the circulation (∼12.6min half-life for recombinant human LF [rhLF] in rats), which limits its therapeutic potential. Therefore, to improve plasma stability, we developed a recombinant human LF (hLF)-immunoglobulin G1 (IgG1) fragment crystallizable domain (Fc) fusion (hLF-hinge-CH2-CH3) expressed in a Chinese Hamster Ovary cell (CHO) expression system and evaluated the in vitro bioactivities and pharmacokinetic properties of the purified fusion. CHO DG44 cells were transfected with an expression vector coding for recombinant hLF-hinge-CH2-CH3. Iron binding, Caco-2 uptake, and thermal stability were investigated in vitro, and pharmacokinetic parameters were investigated in vivo. hLF-hinge-CH2-CH3 was significantly expressed in CHO cells (∼100mg/l culture), was readily purified, and exhibited 98.3% of the non-fused rhLF iron-binding activity. Caco-2 uptake and thermal stability were improved for hLF-Fc fusion relative to rhLF. Moreover, hLF-hinge-CH2-CH3 demonstrated a plasma half-life that was 9.1-fold longer than that of rhLF as well as longer than that of the PEGylated bovine LFs that we previously developed. Thus, CHO-derived hLF-hinge-CH2-CH3, with enhanced pharmacokinetic properties, is a promising candidate drug for potential parenteral administration. |
| Volume | 67 |
| Pages | 136-143 |
| Published | 2015-1-25 |
| DOI | 10.1016/j.ejps.2014.11.005 |
| PII | S0928-0987(14)00433-3 |
| PMID | 25433245 |
| MeSH | Animals CHO Cells Caco-2 Cells Cricetulus Humans Immunoglobulin Fc Fragments* / blood Immunoglobulin Fc Fragments* / genetics Immunoglobulin Fc Fragments* / metabolism Immunoglobulin Fc Fragments* / pharmacology Immunoglobulin G* / blood Immunoglobulin G* / genetics Immunoglobulin G* / metabolism Immunoglobulin G* / pharmacology Intestinal Absorption Iron / metabolism Lactoferrin* / blood Lactoferrin* / genetics Lactoferrin* / metabolism Lactoferrin* / pharmacokinetics Male Rats, Wistar Recombinant Fusion Proteins* / blood Recombinant Fusion Proteins* / genetics Recombinant Fusion Proteins* / metabolism Recombinant Fusion Proteins* / pharmacokinetics |
| IF | 3.616 |
| Times Cited | 7 |
| WOS Category | PHARMACOLOGY & PHARMACY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | CACO-2(RCB0988) |