Self-assembling lisofylline-fatty acid conjugate for effective treatment of diabetes mellitus

Kishan S. Italiya, Samrat Mazumdar, Saurabh Sharma, Deepak Chitkara, Ram I. Mahato, Anupama Mittal

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Lisofylline is an anti-inflammatory agent with proven anti-diabetic activity. Its high solubility and rapid metabolism results in poor bioavailability and short half-life, limiting its clinical utility. We have synthesized Lisofylline-Linoleic acid (LSF-LA) conjugate which self-assembled into micelles (156.9 nm; PDI 0.187; CMC 1 μg/mL; aggregation number 54) without any surfactant and showed enhanced cellular uptake. It protected MIN6 insulinoma cells from cytokine induced cell death and enhanced insulin production under inflammatory conditions. It also suppressed the proliferation of activated peripheral blood mononuclear cells and reduced the production of inflammatory cytokines, IFN-γ and TNF-α. LSF-LA micelles exhibited reduced protein binding, significantly higher half-life (5.7-fold) and higher apparent volume of distribution (5.3-fold) than free LSF. In T1D animals, reduced blood glucose levels were observed at a reduced dose (~15 mg/kg, once daily of LSF-LA micelles vs. 25 mg/kg, twice daily of free LSF) that was further confirmed by immunohistochemical analysis.

Original languageEnglish (US)
Pages (from-to)175-187
Number of pages13
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume15
Issue number1
DOIs
StatePublished - Jan 2019

Keywords

  • Diabetes
  • Linoleic acid
  • Lisofylline
  • Pharmacokinetics
  • Self-assembly

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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