Nucleic acid carriers for pulmonary gene delivery

The delivery of nucleic acids to the pulmonary route appears to be promising due to non-invasiveness, large area of epithelial surface lining the lung, easy accessibility and ability to provide a platform for local delivery. The therapeutic role of nucleic acids in various diseases pertaining to the pulmonary route e.g. cystic fibrosis, α1-antitrypsin deficiency, asthma, chronic obstructive pulmonary disease, lung cancer etc. have been realized due to the increase in the understanding of genetic pathways. Numerous potential therapeutic targets have been explored in pharmacotherapeutics of such pulmonary diseases for gene delivery. Viral and nonviral carrier mediated nucleic acids delivery has been investigated in the field. But gene delivery by viral vectors remains restricted due to their toxicity and immunogenicity. Nucleic acid delivery via nonviral vectors seems attractive to researchers due to safety, ease of synthesis and scale up. Successful delivery of nucleic acids by pulmonary route also remains challenging due to several anatomical and physical barriers, immune response, particle aggregation, etc. For overcoming the various challenges posed for achieving therapeutics benefits from gene delivery via pulmonary route, the problems that need to be addressed includes overcoming the mucus barriers by use of mucolytic agents, mucus penetrating particles; minimizing the immune response, improving in vivo stability, controlled release of the carriers, preventing aggregation of the carriers etc. The current review is focussed providing details on the various delivery strategies for overcoming the barriers for successful delivery and gives brief details on the therapeutic advancements made in the field.