Absorption enhancers in pulmonary protein delivery

Extensive research efforts have been directed towards the systemic administration of therapeutic proteins and poorly absorbed macromolecules via various nontraditional, injection-free administration sites such as the lung. As a portal for noninvasive delivery, pulmonary administration possesses several attractive features including a large surface area for drug absorption. Nevertheless, achieving substantial bioavailability of proteins and macromolecules by this route has remained a challenge, chiefly due to poor absorption across the epithelium. The lungs are relatively impermeable to most drugs when formulated without an absorption enhancer/promoter. In an attempt to circumvent this problem, many novel absorption promoters have been tested for enhancing the systemic availability of drugs from the lungs. Various protease inhibitors, surfactants, lipids, polymers and agents from other classes have been tested for their efficacy in improving the systemic availability of protein and macromolecular drugs after pulmonary administration. The purpose of this article is to provide the reader with a summary of recent advances made in the field of pulmonary protein delivery utilizing absorption enhancers. This report reviews the various agents used to increase the bioavailability of these drugs from the lungs, their mechanisms of action and effectiveness, and their potential for toxicity.