Noncovalent PEGylation of L-Asparaginase Using PEGylated Polyelectrolyte

作者：Kurinomaru Takaaki; Shiraki Kentaro^*

来源：Journal of Pharmaceutical Sciences, 2015, 104(2): 587-592.

DOI：10.1002/jps.24217

• complexation
• pegylation
• polyelectrolytes
• protein aggregation
• protein formulation
• stabilization

Noncovalent PEGylation has great potential for stabilization of therapeutic proteins. Here, we demonstrated that the noncovalent PEGylation with a PEGylated polyelectrolyte stabilized a therapeutic protein, l-asparaginase (ASNase). Anionic ASNase and cationic poly(ethylene glycol)-block-poly(N,N-dimethylaminoethyl methacrylate) (PEG-b-PAMA) formed a water-soluble protein-polyelectrolyte complex (PPC) without loss of secondary structure and enzyme activity. PPC with PEG-b-PAMA successfully inhibited the shaking-induced inactivation and aggregation of ASNase as well as protease digestion, corresponding to the behaviors of covalently PEGylated ASNase. Thus, noncovalent PEGylation by PEGylated polyelectrolytes is a new candidate for handling of therapeutic proteins.

• 出版日期2015-2