Abstract
In this article, applications of engineered nanoparticles containing siRNA for inhalation delivery are reviewed and discussed. Diseases with identified protein malfunctions may be mitigated through the use of well-designed siRNA therapeutics. The inhalation route of administration provides local delivery of siRNA therapeutics to the lungs for various pulmonary diseases. A siRNA delivery system can be used to overcome the barriers of pulmonary delivery, such as anatomical barriers, mucociliary clearance, cough clearance, and alveolar macrophage clearance. Apart from naked siRNA aerosol delivery, previously studied siRNA carrier systems include those of lipidic, polymeric, peptide, or inorganic origin. These delivery systems can achieve pulmonary delivery through the generation of an aerosol via an inhaler or nebulizer. The preparation methodologies for these siRNA nanocarrier systems will be discussed herein. The use of inhalable nanocarrier siRNA delivery systems have barriers to their effective delivery, but overcoming these constraints while formulating a safe and effective delivery system will offer unique advances to the field of inhaled medicine.
Highlights
SiRNA has potential therapeutic applications in treating ‘undruggable’ diseases via post-transcriptional downregulation of target gene expression
This study found that siRNAs sequences shared by human and rodents successfully knocked down TGF-β1 expression in human derived cell lines and significantly inhibited pulmonary fibrosis in vivo
Since aerosolization is a high shear stress process, the stability of the liposomes should be monitored since this process may cause physical and chemical changes that can lead to early siRNA release and degradation of the siRNA (Gaspar M.M. et al, 2008)
Summary
Various promising inorganic delivery systems have been investigated for the delivery of siRNA devised for diagnostic and therapeutic purposes. They include carbon nanotubes and metals such as iron oxide, quantum dots, gold and silica (Chen S. et al, 2014). Mesoporous silica based nanoparticles (MSN) have been widely investigated as carriers for siRNA based targeted drug delivery systems (Chen A.M. et al, 2009; Radu D.R. et al, 2004). The. MSN are chemically stable, safe and biodegradable which makes it a promising gene delivery carrier. MSN possess several advantages over other inorganic carriers, such as capability to encapsulate higher amounts of drugs due to large pore volumes and improved stability due to their inorganic oxide framework (Slowing, Ii et al, 2007)
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