Hybrid hyaluronan hydrogel encapsulating nanogel as a protein nanocarrier: New system for sustained delivery of protein with a chaperone-like function

Tai Hirakura, Kenji Yasugi, Takayuki Nemoto, Mika Sato, Tsuyoshi Shimoboji, Yoshinori Aso, Nobuyuki Morimoto, Kazunari Akiyoshi

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)483-489
Number of pages7
JournalJournal of Controlled Release
Volume142
Issue number3
DOIs
Publication statusPublished - 2010 Mar 19
Externally publishedYes

Keywords

  • hyaluronan
  • hybrid hydrogel
  • nanogel
  • protein delivery
  • sustained release

ASJC Scopus subject areas

  • Pharmaceutical Science

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