Nanomedicine for acute lung injury

Ruxana T Sadikot

Nanomedicine for acute lung injury

Ruxana T Sadikot

Emory University School of Medicine, USA

: J Pharm Drug Deliv Res

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a heterogenous group of lung disease in critically ill patients. Despite the increased understanding of the molecular pathogenesis of ARDS, the mortality remains unacceptably high, ranging from 34% to 64%. Hence, ARDS represents an unmet medical need with an urgency to develop effective pharmacotherapies. Several promising targets that have been identified as potential therapies for ARDS have been limited because of difficulty with delivery. In recent years nanomedicine has become an attractive concept for the targeted delivery of therapeutic and diagnostic compounds to injured or inflamed organs. Nanoscale drug delivery systems have the ability to improve the pharmacokinetics and increase the biodistribution of therapeutic agents to target organs, thereby resulting in improved efficacy and reduced drug toxicity. We have developed novel long-acting biocompatible and biodegradable phospholipid micelles (size, approximately 15 nm) to inhibit triggering receptor expressed on myeloid cells 1 (TREM-1) a key effector that contributes to the pathogenesis of lung injury. Realizing short half-life of peptide drugs (minutes) hampers their clinical use, we invented micellar TREM-1 blocking peptide and glucagon-like peptide-1(7-36) amide (GLP-1) where each peptide drug is stabilized in its active form (alpha-helix) and its bioactivity is prolonged for hours in vivo. These long-acting micellar nanomedicines provide significant advancement in the treatment of experimental ALI which has the potential to be extended to treat patients with this devastating disease.