Dp 4m

In the in vivo deposition experiments, the Cy7-loaded PLGA LPMPs were quickly administered to the rat lung using an insufflator (DP-4M, Penn-Century Inc., PA, USA) through the trachea without anesthesia. To confirm the lung deposition of microparticles, the tissue sections and the whole lung were observed using fluorescence microscopy and the imaging station (IVIS Spectrum CT, Perkin Elmer, US), respectively. The non-large porous PLGA microparticles were used as a control to compare the lung deposition efficiency of the LPMPs.

Rat primary lung cancer models were prepared following pulmonary delivery of MCA and DEN in our laboratory¹⁰ (link). The chemical-induced lung cancer models served as a good simulation of clinical NSCLC induced by toxic agents. Healthy rats and tumor-bearing rats were administered saline (0.2 mL) by spraying saline into the lungs through the trachea with a long soft plastic tube. CPs (1 mg each rat) and LCDs (10 mg each rat, containing 1 mg curcumin) were sprayed into the lungs of tumor-bearing rats using an insufflator (DP-4M, Penn-Century Inc., USA) through the trachea without anesthesia. Gemcitabine solutions (0.1 mL, 10 mg/mL) in saline were also sprayed into the lungs of tumor-bearing rats with a soft plastic tube. All the medications were administered once a day for 4 days, after which the rats were sacrificed and the trachea exposed. The right lung was ligated using a hemostatic clamp. The left lung was flushed with cold saline (4 °C, 4 mL, flushing three times). The acquired BALFs were centrifuged at 3500 rpm (Low Speed Centrifuge, DT5-4B, Beijing Shidai Beili Centrifuge Co., Ltd., Beijing, China) for 15 min and the supernatant was collected for detection of cytokines or markers.