Phospholipids in pulmonary drug delivery

Abstract

Pulmonary delivery is becoming the standard route of administration for treating respiratory disorders such as asthma and chronic obstructive pulmonary disease. It is also gaining interest for non‐invasive systemic delivery of peptides and proteins. A limited number of excipients is approved or authorized for the pulmonary tract. This restricts the commercial potential of some formulations. Phospholipids and more particularly 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine (DPPC) are the main components of lung surfactant and are recognized as generally recognized as safe (GRAS) excipients for pulmonary drug delivery by the Food and Drug Administration. Moreover, phospholipids could modulate the physicochemical properties of drug delivery systems and therefore the drug release and/or dissolution. They can potentially modulate the drug pharmacokinetic by enhancing the drug permeability through the lung epithelium using palmitoyl‐based phospholipids, and/or by reducing recognition of the drug delivery systems by the alveolar macrophages by including DPPC or polyethyleneglycol (PEG) at their surface. Therefore, this review focuses on the formulations containing phospholipids or PEGylated phospholipids, such as micelles, liposomes, lipid micro‐/nanoparticles, large porous particles, solid dispersions, and microparticle suspensions.Drug delivery systems composed mainly or secondarily by phospholipids could be aerosolized by an appropriate device (nebulizer for aqueous‐based formulations, pressurized metered dose inhalers for propellant or aqueous‐based formulations or dry powder inhaler for powder‐based formulations) to be deposited in the lungs following their aerodynamic diameter. Phospholipids included in the drug delivery systems could modulate aerodynamic performances and drug pharmacokinetic.