title: Injectable hydrogel for sustained protein release by salt-induced association of hyaluronic acid nanogel.
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.
authors.affiliation: Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Tokyo, 101-0062, Japan. nakaitks@chugai-pharm.co.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakai
authors.forename: Tai
authors.initials: T
authors.lastname: Hirakura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shimoboji
authors.forename: Masaki
authors.initials: M
authors.lastname: Ishigai
authors.forename: Kazunari
authors.initials: K
authors.lastname: Akiyoshi
mesh_terms: D000818:Animals; D002021:Buffers; D002788:Cholesterol Esters / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004921:Erythropoietin / Q000737:chemistry; D000077270:Exenatide; D013006:Growth Hormone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D020100:Hydrogels; D007267:Injections; D008297:Male; D009113:Muramidase / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D055550:Protein Stability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000737:chemistry; D014688:Venoms / Q000737:chemistry
chemical_list: D002021:Buffers; D002788:Cholesterol Esters; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D010455:Peptides; D014688:Venoms; D004921:Erythropoietin; D012965:Sodium Chloride; D013006:Growth Hormone; D006820:Hyaluronic Acid; D000077270:Exenatide; D009113:Muramidase