Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Sadikot, Ruxana T.; Kolanjiyil, Arun V.; Kleinstreuer, Clement; Rubinstein, Israel

Realizing the short half-life of peptide drugs (minutes) hampers their clinical use, we invented micellar TREM1 peptide and GLP-1, where each peptide drug is stabilized in its active form (α-helix) and its bioactivity is prolonged for hours in vivo. Likewise, the water insolubility of 17-AAG, a selective Hps90 inhibitor, constrains its use in humans. Accordingly, self-association of 17-AAG with these micelles overcomes this limitation while at the same time increasing its stability and bioavailability. These long-acting micellar drugs provided significant advancements in the treatment of experimental of ALI, which could then be extended to critically ill patients. Nanoparticles can be introduced by systemic administration (oral, dermal, intravenous, etc.) or directly into the lung through inhalation or intranasal or oropharyngeal aspiration. Systemic delivery of nanoparticles is based on the principle of passive targeting. Passive targeting occurs as a result of extravasation of the nanoparticles at the diseased site where the microvasculature is leaky as in ARDS [35] .