1. Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2‐3‐10 Kanda‐surugadai, Chiyoda‐ku, Tokyo, 101‐0062, Japan;2. Pre‐clinical Research Department, Chugai Pharmaceutical Co., Ltd., 1‐135 Gotemba, Shizuoka, 412‐8513, Japan;3. Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo‐ku, Kyoto, 615‐8510, Japan
Abstract:
A hyaluronic acid‐based anionic nanogel formed by self‐assembly of cholesteryl‐group‐bearing HA is designed for protein delivery. The HA nanogel spontaneously binds various types of proteins without denaturation, such as recombinant human growth hormone, erythropoietin, exendin‐4, and lysozyme. The HA nanogel shows unique colloidal properties, in particular that an injectable hydrogel is formed by salt‐induced association of the HA nanogel. A pharmacokinetic study in rats shows that an in situ gel formulation, prepared by simply mixing rhGH and HA nanogel in phosphate buffer, maintains plasma rhGH levels within a narrow range over one week. Therefore, HA nanogels offer a simple method for easy formulation of therapeutic proteins and are effective for sustained protein release systems.
