Protein based nanoparticles for pulmonary drug delivery: advances, challenges, and future perspectives

Abstract

Pulmonary drug delivery has been a candidate for the treatment of respiratory disorders with a large surface area, high rate of drug absorption, and prevention of first-pass metabolism. Of the different nanocarrier systems that have been investigated, protein-based nanoparticles (PNPs) are found to possess several distinct advantages, such as superior biocompatibility, biodegradability, high drug loading capacity, and tunable release profiles. Their native tunability provides the flexibility to coat the particle surface with ligands and polymers for receptor-mediated targeting and increased penetration of the mucus. They render PNPs especially well-suited to circumvent biological barriers in the lung, including mucociliary clearance, uptake by alveolar macrophages, and interference by surfactant. Formulation strategies Toefl spray drying, freeze drying, and electrospray membrane have extensively been optimized to improve the aerodynamics and stability of PNPs for inhalation. To further improve multifunctionality, recent advances in protein nanotechnology have allowed the development of multifunctional PNPs that are capable of targeted delivery and stimulus-responsive drug release. These developments notwithstanding, immunogenicity, protein stability, scale-up production, and regulatory approval remain significant hindrances to clinical translation. Further research and development in this field are necessary to realize the complete therapeutic benefit of protein-based nanoparticles in pulmonary drug delivery.