Background: Interferon-α2b is FDA approved drug for the treatment of chronic HCV
and HBV, melanoma, AIDS-related KS, carcinomas, hairy cell leukemia and chronic myelogenous
leukemia. However, administration of interferon-α2b to patients takes place thrice in a week due to
short in vivo circulation half-life.
Objective: To extend the circulation half-life of IFN-α2b, it is conjugated with polyethylene glycol
(PEG). However, PEGylation may results in reduction of its antiviral and antiproliferative activities
but on the other side, it results in prolonged plasma half-life.
Methods: Human interferon-α2b was PEGylated with linear 20kDa methoxypolyethlene glycol
(mPEG) Propionaldehyde (IFN-Ald20K), Y-Shaped 40kDa mPEG-Propionaldehyde (IFNAld40K),
linear 20-kDa mPEG-Succinimidyl Succinate (IFN-NHS20K), and Y shaped 40kDa
mPEG-Succinimidyl Succinate (IFN-NHS40K). Impact of PEG size, shape and PEGylation site
was studied to establish their relationship with antiprolifetaive activities and serum retention time
of PEGylated IFN-α2b.
Result: RP-HPLC studies showed that larger PEGs (40kDa) increased the hydrodynamic volume
and increased the serum retention time while antiproliferative activity in HepG2 cell line was
decreased with increase in PEGylated interferon-α2b size. Molecular docking results also dictated
the same effect that increase in PEGylated interferon-α2b size results in steric shielding of the
receptor-binding site on interferon-α2b. IFN-Ald20K showed highest (45%) biological activity with
serum half-life 40 hours while IFN-NHS40K showed least (7%) biological activity with serum halflife
Conclusion: Thus, IFN-Ald40K with 12% residual activity and 62 hours of serum half-life proved
to be a potent candidate for anticancer and antiviral effect with enhanced serum retention time.