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Multi-Compartmental Nanoparticles-in-Emulsion Formulation for Macrophage-Specific Anti-Inflammatory Gene Delivery

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ABSTRACT

Purpose

To develop a safe and effective non-viral vector for gene delivery and transfection in macrophages for potential anti-inflammatory therapy.

Methods

Solid nanoparticles-in-emulsion (NiE) multi-compartmental delivery system was designed using plasmid DNA-encapsulated type B gelatin nanoparticles suspended in the inner aqueous phase of safflower oil-containing water-in-oil-in-water (W/O/W) multiple emulsion. Control and NiE formulations were evaluated for DNA delivery and transfection efficiency in J774A.1 adherent murine macrophages.

Results

Using green fluorescent protein (GFP) and murine interleukin-10 (mIL-10) expressing plasmid DNA constructs, the NiE formulation was found superior in enhancing intracellular delivery and gene transfection efficiency in cells. Anti-inflammatory effects of transfected mIL-10 were examined by suppression of tumor necrosis factor-alpha (TNFα) and interleukin 1-beta (IL-1β) production in lipopolysaccharide (LPS)-stimulated cells.

Conclusions

Overall, the results were very encouraging towards development of a macrophage-specific NiE-based multi-compartmental gene delivery strategy that can potentially affect a number of acute and chronic inflammatory diseases.

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ACKNOWLEDGMENTS & DISCLOSURES

This study was supported by a grant (R01-DK080477) from the National Institute of Diabetes, Digestive Diseases, and Kidney Diseases of the National Institutes of Health. We deeply appreciate the assistance of Ms. Jing Xu with the transmission electron microscopy analysis that was performed at the Electron Microscopy Center of Northeastern University.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115, USA

    Husain Attarwala & Mansoor Amiji

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  1. Husain Attarwala
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  2. Mansoor Amiji
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Correspondence to Mansoor Amiji.

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Attarwala, H., Amiji, M. Multi-Compartmental Nanoparticles-in-Emulsion Formulation for Macrophage-Specific Anti-Inflammatory Gene Delivery. Pharm Res 29, 1637–1649 (2012). https://doi.org/10.1007/s11095-012-0677-9

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  • DOI: https://doi.org/10.1007/s11095-012-0677-9

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