Inhalable lipid-based nanocarriers covered by polydopamine for effective mucus penetration and pulmonary retention

To overcome the critical challenge in drug inhalation for pulmonary diseases, we innovatively proposed that polydopamine (PDA) as a surface modification material had great potential to improve the mucus permeation and pulmonary retention of inhalable lipid-based nanocarriers. We prepared PDA coated lipid nanoemulsions/solid lipid nanoparticles/liposomes and systematically evaluated their interactions with mucin and pulmonary retention after inhalation. PDA-coated lipid-based nanocarriers exhibited weaker interactions with mucins, higher mucus permeability and cellular uptake by the respiratory epithelium cells compared to PEGylated lipid-based nanocarriers. However, the pulmonary retention advantage of PDA coating was shown in lipid nanoemulsions (< 50 nm) and solid lipid nanoparticles (< 100 nm). Liposomes (∼ 150 nm) with PEGylation possessed higher pulmonary retention than that coated by PDA. It was suggested that PEGylated liposomes were liable to be phagocytosed by alveolar macrophages due to binding with specific antibodies. Overall, this work suggests that PDA as a surface modification material of inhalable lipid-based nanocarriers holds promise for effective mucus penetration and pulmonary retention.