Chitosan Nanoparticles in Pulmonary Drug Delivery: Unleashing the Potential for Targeted and Effective Therapy.

Pulmonary drug delivery is used for local treatment of lung diseases and for systemic administration of drugs requiring rapid absorption. Drug delivery to the lungs is limited by mucociliary clearance, macrophage uptake, and short residence time of inhaled formulations. Polymer-based carrier systems have therefore been explored to improve lung retention and delivery efficiency. Chitosan, a polysaccharide obtained from chitin, is biodegradable, biocompatible, and positively charged, enabling interaction with negatively charged pulmonary mucus. When formulated as nanoparticles, chitosan allows modulation of particle size, surface charge, and drug release behavior, which are critical parameters for pulmonary deposition. Chitosan nanoparticles have been investigated for delivery of small molecules, proteins, and nucleic acids in respiratory infections, inflammatory lung diseases, and lung cancer. Reported studies demonstrate improved lung localization and sustained drug release compared with conventional formulations. This review summarizes formulation approaches used for the preparation of chitosan nanoparticles for pulmonary delivery and discusses key physicochemical factors influencing their performance. Limitations related to aerosolization behavior and formulation reproducibility are also considered.