Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord

Ellen C. Dengler, Juewen Liu, Audra Kerwin, Sergio Torres, Clara M. Olcott, Brandi N. Bowman, Leisha Armijo, Katherine Gentry, Jenny Wilkerson, James Wallace, Xingmao Jiang, Eric C. Carnes, C. Jeffrey Brinker, Erin D. Milligan

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

Amorphous mesoporous silica nanoparticles ('protocells') that support surface lipid bilayers recently characterized in vitro as carrier constructs for small drug and DNA delivery are reported here as highly biocompatible both in vitro and in vivo, involving the brain and spinal cord following spinal delivery into the lumbosacral subarachnoid space (intrathecal; i.t.). Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP)-cholesterol (DOTAP:Chol) liposome-formulated protocells revealed stable in vitro cargo release kinetics and cellular interleukin-10 (IL-10) transgene transfection. Recent approaches using synthetic non-viral vector platforms to deliver the pain-suppressive therapeutic transgene, IL-10, to the spinal subarachnoid space have yielded promising results in animal models of peripheral neuropathy, a condition involving aberrant neuronal communication within sensory pathways in the nervous system. Non-viral drug and gene delivery protocell platforms offer potential flexibility because cargo release-rates can be pH-dependent. We report here that i.t. delivery of protocells, with modified chemistry supporting a surface coating of DOTAP:Chol liposomes and containing the IL-10 transgene, results in functional suppression of pain-related behavior in rats for extended periods. This study is the first demonstration that protocell vectors offer amenable and enduring in vivo biological characteristics that can be applied to spinal gene delivery.

Original languageEnglish (US)
Pages (from-to)209-224
Number of pages16
JournalJournal of Controlled Release
Volume168
Issue number2
DOIs
StatePublished - Jun 10 2013
Externally publishedYes

Keywords

  • Biocompatibility
  • Cell and tissue viability
  • Gene delivery
  • Interleukin-10 cytokine
  • Neuropathic pain
  • Non-viral vector

ASJC Scopus subject areas

  • Pharmaceutical Science

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