Muco-adhesive chitosan-coated polyphenol nanoparticle for treatment of infectious acute pneumonia through sustained pulmonary delivery of polymyxin B.

Infectious acute pneumonia caused by bacteria has been a great challenge to human health for long time, and the rapid clearance of aerosolized antibiotics in the lungs restricts their clinical application. The development of nanoformulations with facile preparation and mucoadhesive properties for the pulmonary delivery of antibiotics is thus significant for the treatment of infectious acute pneumonia. In this study, FDA (Food and Drug Administration)-approved tannic acid (TA) was used to construct mucoadhesive nanoformulations through the facile coating of chitosan (CS) to achieve long-lasting anti-infection effects against infectious acute pneumonia. Using an antibacterial peptide, polymyxin B (PB), as the model drug, the flash nanocomplexation technique was used to prepare CS-coated TA/poly(vinyl alcohol) (PVA)/PB nanoparticles (TPBC NPs) through non-covalent interactions of each component. Investigation on acute pneumonia mice model demonstrated that, through the strong electrostatic interaction between positively charged chitosan and negatively charged mucin in the trachea, the release of polymyxin B retained in the lung for at least 24 h-post inhalation of TPBC NPs, thereby inhibiting pulmonary infection within 3 days. Combined with their great biocompatibility, mucoadhesive TPBC NPs prepared by a facile and reproducible procedure may provide a new strategy for the pulmonary delivery of antibiotics to treat infectious acute pneumonia.