Table 1
From the following article
Albinterferon
-2b: a genetic fusion protein for the treatment of chronic hepatitis C
G Mani Subramanian, Michele Fiscella, Araba Lamousé-Smith, Stefan Zeuzem & John G McHutchison
Nature Biotechnology 25, 1411 - 1419 (2007) Published online: 7 December 2007
doi:10.1038/nbt1364
Table 1. Currently available approaches to enhance polypeptide pharmacokinetics
| Approach | Advantages | Challenges | Examples |
|---|---|---|---|
| Chemical/covalent modification | Increased in vivo half-life | Decreased tissue uptake | PEGylation (PEG-hGH7, PEG-IFN- 18 and PEG-IFN- -2b9), albumin and fatty acid acylated insulin13 |
Protection from degradation | Immunogenicity | ||
Reduced renal clearance | Functional heterogeneity | ||
Increased solubility/stability | Maintenance of functional activity; depends on chemistry used | ||
| Microsphere/nanoparticle delivery | Sustained/targeted drug release | Encapsulation efficiency | Poly l-Glu nanoparticle, IFN- -XL6, poly(lactic-co-glycolic acid) (PLGA) microsphere, IFN- 19, human growth hormone5 and PEG-insulin12 |
Protection from degradation | Efficiency of drug release from microspheres | ||
Functional heterogeneity | |||
Maintenance of functional activity | |||
| Protease-resistant variants | Improved stability | Maintenance of functional activity | Ala20Pro-RNaseA14, MART-1 with
amino acid substitution11, T-cell mimotopes22 and G15A growth hormone releasing hormone20 |
Protection from degradation | Immunogenicity | ||
| Albumin fusion | Increased in vivo half-life | Maintenance of functional activity | alb-IFN- 4, alb-GLP-1, alb-insulin8, alb-GH16, alb-IL-215 and alb-BNP21 |
No modification required | Immunogenicity | ||
Design flexibility | |||
Reduced renal clearance | |||
Increased solubility/stability |

Increased in vivo half-life