Modification with polysialic acid-PEG copolymer as a new method for improving the therapeutic efficacy of proteins

Abstract

A new protein derivatization method was developed with a block copolymer to reduce the immunogenicity of therapeutic proteins. The block copolymer consisted of polyethylene glycol (PEG) and polysialic acid (PSA), a nonimmunogenic and biodegradable biopolymer. Uricase was used as a model protein. Molecular weight analysis results indicated that the uricase-PEG-PSA conjugate was linked with 2.5 copolymers for each uricase unit. The residual enzyme activity of the uricase with modification by the PEG-PSA copolymer was 72.4%. The tolerance and stability to heat, acid, alkaline, and trypsin treatments significantly improved compared with the native uricase. The immunogenicity of uricase modified with PEG-PSA copolymer was remarkably reduced. The transmission electron microscopy results of the uricase-PEG-PSA conjugate showed a spherical hydrated shell with a larger particle size. These findings proved that the PSA-PEG-protein conjugate is a formulation that can potentially be used to deliver the protein and peptide-based drugs.

Keywords: Block copolymer; immunogenicity; polyethylene glycol; polysialic acid; uricase.