Table 1


From the following article

Albinterferon alpha-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

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Table 1. Currently available approaches to enhance polypeptide pharmacokinetics

ApproachAdvantagesChallengesExamples
Chemical/covalent modificationfilled circle Increased in vivo half-lifefilled circleDecreased tissue uptakePEGylation (PEG-hGH7, PEG-IFN-beta18 and PEG-IFN-alpha-2b9), albumin and fatty acid acylated insulin13
 filled circle Protection from degradationfilled circle Immunogenicity 
 filled circle Reduced renal clearancefilled circle Functional heterogeneity 
 filled circle Increased solubility/stabilityfilled circle Maintenance of functional activity; depends on chemistry used 
Microsphere/nanoparticle deliveryfilled circle Sustained/targeted drug releasefilled circle Encapsulation efficiencyPoly l-Glu nanoparticle, IFN-alpha-XL6, poly(lactic-co-glycolic acid) (PLGA) microsphere, IFN-alpha19, human growth hormone5 and PEG-insulin12
 filled circle Protection from degradationfilled circle Efficiency of drug release from microspheres 
  filled circle Functional heterogeneity 
  filled circle Maintenance of functional activity 
Protease-resistant variantsfilled circle Improved stabilityfilled circle Maintenance of functional activityAla20Pro-RNaseA14, MART-1 with beta amino acid substitution11, T-cell mimotopes22 and G15A growth hormone releasing hormone20
 filled circle Protection from degradationfilled circle Immunogenicity 
Albumin fusionfilled circle Increased in vivo half-lifefilled circle Maintenance of functional activityalb-IFN-alpha4, alb-GLP-1, alb-insulin8, alb-GH16, alb-IL-215 and alb-BNP21
 filled circle No modification requiredfilled circle Immunogenicity 
 filled circle Design flexibility  
 filled circle Reduced renal clearance  
 filled circle Increased solubility/stability  
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