Pulmonary delivery of therapeutic siRNA.


:Small interfering RNA (siRNA) has a huge potential for the treatment or prevention of various lung diseases. Once the RNA molecules have successfully entered the target cells, they could inhibit the expression of specific gene sequence through RNA interference (RNAi) mechanism and generate therapeutic effects. The biggest obstacle to translating siRNA therapy from the laboratories into the clinics is delivery. An ideal delivery agent should protect the siRNA from enzymatic degradation, facilitate cellular uptake and promote endosomal escape inside the cells, with negligible toxicity. Lung targeting could be achieved by systemic delivery or pulmonary delivery. The latter route of administration could potentially enhance siRNA retention in the lungs and reduce systemic toxic effects. However the presence of mucus, the mucociliary clearance actions and the high degree branching of the airways present major barriers to targeted pulmonary delivery. The delivery systems need to be designed carefully in order to maximize the siRNA deposition to the diseased area of the airways. In most of the pulmonary siRNA therapy studies in vivo, siRNA was delivered either intratracheally or intranasally. Very limited work was done on the formulation of siRNA for inhalation which is believed to be the direction for future development. This review focuses on the latest development of pulmonary delivery of siRNA for the treatment of various lung diseases.


Adv Drug Deliv Rev


Lam JK,Liang W,Chan HK




Has Abstract


2012-01-01 00:00:00














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