Polypseudorotaxane-based supramolecular hydrogels consisting of cyclodextrins and Pluronics as stabilizing agents for antibody drugs

• Published in: Carbohydrate polymers 2021-03, Vol.256, p.117419-117419, Article 117419
• Main Authors: Ohshita, Naoko, Motoyama, Keiichi, Iohara, Daisuke, Hirayama, Fumitoshi, Taharabaru, Toru, Watabe, Naoki, Kawabata, Youhei, Onodera, Risako, Higashi, Taishi
• Format: Article
• Language: English
• Subjects: Antibodies - chemistry; Antibody; Biocompatible Materials - chemistry; Chemistry, Pharmaceutical - instrumentation; Cyclodextrin; Cyclodextrins - chemistry; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Excipients - chemistry; Humans; Hydrogel; Hydrogels - chemistry; Immunoglobulin G - chemistry; Light; Oligosaccharides - chemistry; Particle Size; Pluronic; Poloxamer - chemistry; Polymers - chemistry; Polypseudorotaxane; Rotaxanes - chemistry; Scattering, Radiation; Spectrum Analysis, Raman; Stability; Viscosity; X-Ray Diffraction
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2020.117419

[Display omitted] •Few stabilizing agents stabilize antibody against both thermal and shaking stresses.•PpRX hydrogels stabilized antibody against both thermal and shaking stresses.•The stabilizing effects of the PpRX hydrogels were greater than common gels.•Components of the PpRX hydrogels are biocompatible and low cost.•PpRX hydrogels were prepared by only mixing CyD and pluronics. Recently, antibody drugs have been used worldwide, and based on worldwide sales, 7 of the top 10 pharmaceutical products in 2019 were antibody-based drugs. However, antibody drugs often form aggregates upon thermal and shaking stresses with few efficient stabilizing agents against both stresses. Herein, we developed polypseudorotaxane (PpRX) hydrogels consisting of cyclodextrins (CyDs) and polyethylene glycol (PEG)-polypropylene glycol (PPG)-PEG block copolymers (Pluronics F108, F87, F68, and L44), and evaluated their utility as antibody stabilizing agents. α- and γ-CyDs formed PpRX hydrogels with Pluronics, where CyD/F108 gels showed remarkable stabilizing effects for human immunoglobulin G (IgG) against both thermal and shaking stresses beyond CyD/PEG gels or generic gels. The effects were probably due to the interaction between IgG and the free PPG block of Pluronic F108, resulting in the strong IgG retention in the gels. These findings suggest the great potential of CyD/Pluronic gels as pharmaceutical materials for antibody formulations.