Development and Characterization of Novel Lung Surfactant Vesicles for Targeted Lung Cancer Drug Delivery

Nisha Kakwani, Andrea Gonsalves, Jyothi U. Menon

Lung cancer is the third most common cancer that is usually diagnosed at an advanced stage and with the highest cancer-related mortalities globally, resulting in an urgent need for an effective treatment regimen upon diagnosis. Pulmonary drug delivery is most advantageous in the treatment of respiratory illness. Lipid nanovesicles are the most frequently used drug carriers due to the biocompatibility, ease of preparation and delivery of both hydrophilic and hydrophobic drugs to the targeted site. However, the dynamic environment of the lungs results in active phagocytosing of any foreign particles by the alveolar macrophages entering the respiratory tract. Infasurf® derived from calf-lung surfactant is composed of a mixture of phospholipids, neutral lipids and surfactant proteins that has composition similar to the human LS. However, their ability to form stable and effective drug carrier vesicles is not known. The present work focuses on developing and investigating physicochemical properties and in vitro therapeutic efficacy of the nano LS vesicles (LSVs). LSVs were successfully fabricated having a particle size, ζ potential and polydispersity index (PDI) of 157.3 nm, -51.4 mV and 0.269 respectively. FTIR analysis confirmed the structural integrity of the LSVs and they were found to be stable at both 4 °C and 37 °C for at least 7 days. The extruder efficiency for preparing LSVs were found to be 91.45 ± 4.40 %. Blank LSVs were found to be cytocompatible while cell uptake study displayed a lower uptake of LSVs by NR8383 as compared to the A549 cell lines. In summary, LSVs were able to form stable and effective drug carrier vesicles for pulmonary delivery of therapeutics.