Polysaccharide nanogel delivery of a TNF-α and RANKL antagonist peptide allows systemic prevention of bone loss

Neil Alles, Niroshani S. Soysa, MD Anower Hussain, Nobuyoshi Tomomatsu, Hiroaki Saito, Roland Baron, Nobuyuki Morimoto, Kazuhiro Aoki, Kazunari Akiyoshi, Keiichi Ohya

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

We report here a nanogel-mediated peptide drug delivery system. Low stability is a major drawback towards clinical application of peptide drugs. The W9-peptide, a TNF-α and RANKL antagonist, was used as a model for testing the feasibility of cholesterol-bearing pullulan (CHP)-nanogel as the drug delivery system. We found CHP-nanogel could form complex with the W9-peptide and prevents its aggregation in vitro. Murine bone resorption model using low dietary calcium was used to investigate the in vivo effect. Two-time-injection of 24 mg/kg W9-peptide per day with or without CHP-nanogel was given for 7 days. Thereafter, radiological, and histological assessments were performed. The injections of the W9-peptide (24 mg/kg) with CHP-nanogel prevented the reduction in bone mineral density whereas the same dose without CHP-nanogel could not show any inhibitory effect. Histomorphometric analysis of tibiae showed significant decrease of osteoclast number and surface in CHP-W9 complex treated group and the levels of urinary deoxypyridinoline reflected these decrease of bone resorption parameters. Taken together these data shows that CHP-nanogel worked as a suitable carrier for the W9-peptide and it prevented aggregation and increased the stability of the W9-peptide. This study reveals the feasibility of CHP-nanogel-mediated peptide delivery in preventing bone resorption in vivo.

Original languageEnglish
Pages (from-to)83-88
Number of pages6
JournalEuropean Journal of Pharmaceutical Sciences
Volume37
Issue number2
DOIs
Publication statusPublished - 2009 May 12
Externally publishedYes

Keywords

  • Aggregation
  • Cholesterol-bearing pullulan
  • Drug delivery system
  • Nanogel
  • Peptide drugs
  • Stability

ASJC Scopus subject areas

  • Pharmaceutical Science

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