Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8514266 | Journal of Pharmaceutical Sciences | 2017 | 32 Pages |
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.
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Authors
Taishi Higashi, Naoko Ohshita, Tatsunori Hirotsu, Yoshihito Yamashita, Keiichi Motoyama, Sawako Koyama, Ruriko Iibuchi, Takayuki Uchida, Shiuhei Mieda, Kenji Handa, Tomoaki Kimoto, Hidetoshi Arima,