The Influence of Natural Pulmonary Surfactant on The Efficacy of siRNA-Loaded Dextran Nanogels

Abstract

Aim: Topical administration of siRNA nanocarriers is a promising approach in the treatment of pulmonary disorders. Pulmonary surfactant, covering the entire alveolar surface of mammalian lungs, will be one of the first interfaces that siRNA nanocarriers encounter upon inhalation therapy. Therefore, it is of outstanding importance to evaluate the impact of pulmonary surfactant on the performance of siRNA nanocarriers. Materials & methods: The effect of natural lung-derived surfactants on the siRNA delivery capacity of dextran nanogels (DEX-NGs) was evaluated in vitro using flow cytometry and confocal microscopy. Results: Although the interaction with pulmonary surfactant decreases the cellular internalization of siRNA-loaded DEX-NGs significantly, the gene silencing potential of siRNA-loaded DEX-NGs was maintained. On the other hand, cationic lipid-based siRNA nanocarriers (Lipofectamine™ RNAiMAX) were incompatible with pulmonary surfactants. Conclusion: Our data suggest that pulmonary surfactant can enhance the intracellular siRNA delivery by DEX-NGs, thereby possibly providing new therapeutic opportunities.

Original submitted 18 April 2012; Revised submitted 14 September 2012; Published online 18 February 2013

Keywords::

• Curosurf^®
• dextran nanogel
• Infasurf^®
• lipoplex
• polymeric nanoparticle
• pulmonary surfactant
• siRNA delivery

Financial & competing interests disclosure

L De Backer is a doctoral fellow of the Special Research Fund – Ghent University (BOF). K Raemdonck is a postdoctoral fellow of the Research Foundation-Flanders, Belgium (FWO-Vlaanderen). Financial support of the Special Research Fund – Ghent University (BOF12/GOA/014) is also gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors would like to thank K Smets from the Department of Neonatology, Ghent University Hospital (Belgium), for his collaboration. Chiesi Pharmaceuticals (Italy) and ONY, Inc. (NY, USA) are acknowledged for the supply of Curosurf^® and Infasurf^®.

Additional information

Funding

L De Backer is a doctoral fellow of the Special Research Fund – Ghent University (BOF). K Raemdonck is a postdoctoral fellow of the Research Foundation-Flanders, Belgium (FWO-Vlaanderen). Financial support of the Special Research Fund – Ghent University (BOF12/GOA/014) is also gratefully acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.