Currently, there is no specific treatment for acute lung injury (ALI) in clinical practice. In order to efficiently and accurately treat ALI, the advantages of cationic carriers were combined to accelerate the cell uptake. Polycaprolactone-polyethylene glycol carrier (PCL-PEG-COOH, PPC) with good biocompatibility, polycaprolactone-polyethylmethacrylate cationic carrier (PCL-PDMAEMA, PCD), and polycaprolactone-polyethylene glycol carrier connected with high-affinity targeting peptide (Esbp) targeting inflammatory endothelial cells (PCL-PEG-Esbp, PPE) were used to construct the high-molecular polymer micelles (PCD/PPC/PPE). The particle size of the prepared DEX-loaded micelles was 130 ± 4.41 nm, and the Zeta potential was 28.3 ± 0.76 mV. The CMC value of the prepared polymer micelles was 0.643 μg/mL, and it was not easy to depolymerize in the blood circulation. Only about 40% DXM was released from the drug-loaded polymer micelles after 12 h compared with free DXM, indicating that the micelle material had a certain sustained-release performance in vitro release experiments. The safe concentration range of polymer was determined by biocompatibility test. It was recommended that the concentration of polymer micelles should not exceed 0.40 mg/mL to obtain a good compatibility in organisms. The results of cytotoxicity measurement showed that when the content of PCD increased to 50%, the concentration of blank micelles should not exceed 500 μg/mL and the concentration of DXM-loaded micelles should not be higher than 100 μg/mL. It was proved in the cell uptake experiment that the cation carrier of the micelles accelerated the cell uptake. The targeting ability of the targeted micelle group was higher compared with the non-targeted micelle group (P < 0.01, **). Meanwhile, the targeting ability of the non-targeted micelle group was higher compared with the free group (P < 0.001, ***). The targeting ability of the non-targeted micelle group was about 2.30 times and the targeted micelle group was about 3.16 times larger than that of the free group. It was also proved in the in vivo targeting experiments that the targeted micelles had a good targeting ability. The results of in vivo imaging of mice showed that the DXM of the micelle group gathered more in the lungs, and the micelle group had a better targeting ability compared with the free DID group. The order of lung targeting intensity was targeted micelles > non-targeted micelles >> free DID group. The targeting ability of polypeptide Esbp to ALI was confirmed. In conclusion, the prepared PCD/PPC/PPE polymer micelles had obvious in vitro and in vivo targeting ability and good biocompatibility. They could be used as a new targeted delivery system for the treatment of ALI in the future.
Keywords: E-selectin-binding peptides; acute lung injury; cationic polymers; drug targeting; polymer micelles.