Polyrotaxane-Based Supramolecular Material for Improvement of Pharmaceutical Properties of Protein Drugs

Abstract

Pharmaceutical excipients, such as surfactants, amino acids, and polymers, have often been used to improve the physicochemical properties of protein drugs. However, the effects of these additives are limited because of factors such as their weak interactions with protein drugs. In the present study, we evaluated the application of a supramolecular polymer, aminated polyrotaxane (NH₂-PRX), which can strongly interact with protein drugs via its dynamic and transformable properties, as a new pharmaceutical excipient for these agents. As a conventional control polymer with low mobility and average complexation ability, aminated dextran (NH₂-DEX) was also prepared. NH₂-PRX significantly reduced the aggregation of antibodies induced by shaking, compared with NH₂-DEX. The adsorption of insulin onto glass and polypropylene containers was also reduced by the addition of NH₂-PRX. In addition, the in vivo bioactivity of insulin was completely retained in the presence of NH₂-PRX. Moreover, severe adverse effects were not observed following the administration of NH₂-PRX. These findings indicate the potential use of NH₂-PRX as a transformable pharmaceutical excipient for protein drugs.

Keywords: Adsorption; Antibody; Cyclodextrin; Insulin; Polyethylene glycol; Stability.