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

JOURNAL OF CONTROLLED RELEASE

卷:168

Article

Dengler, Ellen C.¹  Liu, Juewen²  Kerwin, Audra¹  Torres, Sergio¹  Olcott, Clara M.¹  Bowman, Brandi N.¹  Armijo, Leisha¹  Gentry, Katherine³  Wilkerson, Jenny¹  Wallace, James¹  Jiang, Xingmao²  Carnes, Eric C.²  Brinker, C. Jeffrey²  Milligan, Erin D.⁴ 

[1] Univ New Mexico, Hlth Sci Ctr, Dept Neurosci, Albuquerque, NM 87131 USA

[2] Univ New Mexico, Dept Chem & Nucl Engn, Albuquerque, NM 87131 USA

[3] Univ New Mexico, Dept Anesthesiol & Crit Care Med, Hlth Sci Ctr, Albuquerque, NM 87131 USA

[4] Univ New Mexico, Sch Med, Dept Neurosci, Hlth Sci Ctr, Albuquerque, NM 87131 USA

关键词: Interleukin-10 cytokine;    Gene delivery;    Biocompatibility;    Neuropathic pain;    Cell and tissue viability;    Non-viral vector;   

DOI  :  10.1016/j.jconrel.2013.03.009

来源: Elsevier

【 摘 要 】

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. (C) 2013 Elsevier B.V. All rights reserved.

【 授权许可】

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