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Purpose. Nanoparticles are able to enhance drug or DNA stability for purposes of optimised deposition to targeted tissues. Surface modifications can mediate drug targeting. The suitability of nanoparticles synthesised out of porcine gelatin, human serum albumin, and polyalkylcyanoacrylate as drug and gene carriers for pulmonary application was investigated in vitro on primary airway epithelium cells and the cell line 16HBE14o-. Methods. The uptake of nanoparticles into these cells was examined by confocal laser scan microscopy (CLSM) and flow cytometry (FACS). Further the cytotoxicity of nanoparticles was evaluated by an LDH-release-test and the inflammatory potential of the nanoparticles was assessed by measuring IL-8 release. Results. CLSM and FACS experiments showed that the nanoparticles were incorporated into bronchial epithelial cells provoking little or no cytotoxicity and no inflammation as measured by IL-8 release. Conclusions. Based on their low cytotoxicity and the missing inflammatory potential in combination with an efficient uptake in human bronchial epithelial cells, protein-based nanoparticles are suitable drug and gene carriers for pulmonary application. [Copyright &y& Elsevier]

Air pollution can highly impact the respiratory system in healthy individuals. Studies have indicated that particles with an aerodynamic diameter of ≤2.5 µm (PM2.5) can be considered to be harmful for lung alveoli and bronchial epithelium cells. PM2.5 can be directly inhaled and can deeply penetrate into the lung alveoli, causing lung dysfunction. However, the toxicological mechanism mediated by PM2.5 for respiratory disease has still not been clearly determined. The purpose of the current study was to investigate the effects of PM2.5 on mouse bronchial epithelium cells (MBECs) and explored the possible mechanism mediated by PM2.5 in MBECs. The results of the current study indicated that PM2.5 markedly decreased lung function, including total lung capacity, residual volume, vital capacity and airway resistance in experimental mice. The results demonstrated that PM2.5 markedly induced inflammatory responses, oxidative injury and MBEC apoptosis. PM2.5 increased interleukin (IL)-1β and IL-6 expression, and reactive oxygen species production in MBECs. Furthermore, PM2.5 specifically induced PI3K, AKT and mTOR expression in MBECs. Disruption of PI3K/AKT/mTOR signaling was also indicated to effectively inhibit apoptosis of MBECs. In conclusion, the results of the current study systematically demonstrated the role of apoptosis-mediated MBEC apoptosis in PM2.5-treated mice, and provides a potential strategy for preclinical intervention in patients with PM2.5-induced lung diseases. [ABSTRACT FROM AUTHOR]