Hybrid hyaluronan hydrogel encapsulating nanogel as a protein nanocarrier: new system for sustained delivery of protein with a chaperone-like function.
Novel hybrid hyaluronan (HA) hydrogel encapsulating nanogels was designed for sustained delivery of protein. HA modified with 2-aminoethyl methacrylate was cross-linked via Michael addition in the presence of cholesteryl group-bearing pullulan (CHP) nanogels. The nanogels were physically entrapped and well dispersed in a three-dimensional network of chemically cross-linked HA (HA gel). Therapeutic peptides and proteins, such as glucagon-like peptide-1, insulin and erythropoietin, were spontaneously trapped in the CHP nanogels in the HA gel just by immersing hybrid hydrogels into the drug solutions. CHP/protein complex nanogels were released from the hybrid hydrogels in a sustained manner both in vitro and in vivo. The release was controlled by the cross-linking density and the degradability of the HA gel, modulated by the initial gelation condition. The synergy between the CHP nanogel as a drug reservoir and the HA gel as a nanogel-releasing matrix of the hybrid hydrogel system simultaneously achieved both simple drug loading and controlled release with no denaturation of the protein drugs. This is a new method of fabricating biodegradable controlled release matrix with molecular chaperone-like activity for therapeutic proteins.
Hirakura
Tai
T
Institute of Biomaterial and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, 101-0062, Japan. hirakurati@chugai-pharm.co.jp
Yasugi
Kenji
K
Nemoto
Takayuki
T
Sato
Mika
M
Shimoboji
Tsuyoshi
T
Aso
Yoshinori
Y
Morimoto
Nobuyuki
N
Akiyoshi
Kazunari
K
D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry*; D007275:Injections, Intravenous; D008297:Male; D046529:Microscopy, Electron, Transmission; D018832:Molecular Chaperones / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D049329:Nanostructures / Q000737:chemistry*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D012995:Solubility; D013499:Surface Properties
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D018832:Molecular Chaperones; D010446:Peptide Fragments; D011994:Recombinant Proteins; D006820:Hyaluronic Acid