Opportunities and Challenges for Inhalable Nanomedicine Formulations in Respiratory Diseases: A Review

Abstract

Lungs experience frequent interactions with the external environment and have an abundant supply of blood; therefore, they are susceptible to invasion by pathogenic microorganisms and tumor cells. However, the limited pharmacokinetics of conventional drugs in the lungs poses a clinical challenge. The emergence of different nano-formulations has been facilitated by advancements in nanotechnology. Inhaled nanomedicines exhibit better targeting and prolonged therapeutic effects. Although nano-formulations have great potential, they still present several unknown risks. Herein, we review the (1) physiological anatomy of the lungs and their biological barriers, (2) pharmacokinetics and toxicology of nanomaterial formulations in the lungs; (3) current nanomaterials that can be applied to the respiratory system and related design strategies, and (4) current applications of inhaled nanomaterials in treating respiratory disorders, vaccine design, and imaging detection based on the characteristics of different nanomaterials. Finally, (5) we analyze and summarize the challenges and prospects of nanomaterials for respiratory disease applications. We believe that nanomaterials, particularly inhaled nano-formulations, have excellent prospects for application in respiratory diseases. However, we emphasize that the simultaneous toxic side effects of biological nanomaterials must be considered during the application of these emerging medicines. This study aims to offer comprehensive guidelines and valuable insights for conducting research on nanomaterials in the domain of the respiratory system.

Graphical Abstract

Keywords:

• nanoparticles
• respiratory system
• lungs
• nanomaterials
• nanotechnology

Abbreviations

ALK, Anaplastic lymphoma kinase; ALI, Acute lung injury; AM, Alveolar macrophages; APC, Antigen-presenting cells; CF, Cystic fibrosis; CFTR, CF transmembrane conductance regulator; COPD, Chronic obstructive pulmonary disease; CT, Computed tomography; EGFR, Epidermal growth factor receptor-tyrosine; EPR, Enhanced permeability and retention; hAFS, Human amniotic fluid stem; LHRH, Luteinizing hormone-releasing hormone; LMNP, Lignin micro-/nanoparticles; LN, Lymph nodes; LPN, Liposomal polymer nanoparticles; MPI, Magnetic particle imaging; MRI, Magnetic resonance imaging; NLC, Nanostructured lipid carriers; PAH, Polycyclic aromatic hydrocarbons; PEI, Polyethylene imine; PS, Pulmonary surfactant; ROS, Reactive oxygen species; RSV, Respiratory syncytial virus; SLN, Solid lipid nanoparticles; VARID, Viral Associated Respiratory Infectious Diseases; VOC, Volatile organic compounds.

Consent for Publication

All authors have read and approved the manuscript for submission.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting or writing, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for the contents of this article.

Disclosure

The authors declare no competing interests.

Additional information

Funding

This work was supported by the Ministry of Science and Technology of the People’s Republic of China (STI2030-Major Projects2021ZD0201900) and was supported by National Natural Science Foundation of China (82170100, 82120108002).