title: Stabilizing Effects for Antibody Formulations and Safety Profiles of Cyclodextrin Polypseudorotaxane Hydrogels.
abstract: Antibodies often have poor physicochemical stability during storage and transport, which is a serious drawback for the development of antibody-based drugs. In this study, we prepared polypseudorotaxane (PPRX) hydrogels consisting of cyclodextrins (CyDs) and polyethylene glycol, and evaluated them as stabilizers for commercially available antibody-based drugs. α-CyD and γ-CyD formed PPRX hydrogels with polyethylene glycol (molecular weight 20,000 Da) in the presence of antibody-based drugs such as omalizumab, palivizumab, panitumumab, and ranibizumab. Importantly, both α- and γ-CyD PPRX hydrogel formulations provided high stabilizing effects (ca. 100%) to the all antibody-based drugs used in this study. Furthermore, approximately 100% of the binding activity of omalizumab to the immunoglobulin E receptor was retained after the release from the hydrogels. Plasma levels of omalizumab after subcutaneous injection of the γ-CyD PPRX hydrogel to rats were equivalent to those of omalizumab alone. According to the results of blood chemistry tests, the weights of organs and histological observations α- and γ-CyD PPRX hydrogels induced no serious adverse effects. These results suggest that CyD PPRX hydrogels are useful as safe and promising stabilizing formulations for antibody-based drugs.
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Taishi
authors.initials: T
authors.lastname: Higashi
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Kumamoto, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ohshita
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Kumamoto, Japan.
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Hirotsu
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.affiliation: Terumo Corporation, R&D Headquarters, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Koyama
authors.affiliation: Terumo Corporation, R&D Headquarters, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Ruriko
authors.initials: R
authors.lastname: Iibuchi
authors.affiliation: Terumo Corporation, R&D Headquarters, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Terumo Corporation, R&D Headquarters, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Shiuhei
authors.initials: S
authors.lastname: Mieda
authors.affiliation: Terumo Corporation, R&D Headquarters, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Handa
authors.affiliation: Terumo Corporation, R&D Headquarters, 1500 Inokuchi, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0151, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kimoto
authors.affiliation: Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Kumamoto, Japan. Electronic address: arimah@gpo.kumamoto-u.ac.jp.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000378:metabolism; D003505:Cyclodextrins / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004339:Drug Compounding; D004355:Drug Stability; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D043862:Rotaxanes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003505:Cyclodextrins; D020100:Hydrogels; D043862:Rotaxanes
keywords: complexation; cyclodextrins; hydrogels; monoclonal antibody; physical stability