1. Self-assembled polymeric micelles for combined delivery of anti-inflammatory gene and drug to the lungs by inhalation
- Author
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Jungju Oh, Gyeungyun Kim, Chunxian Piao, and Minhyung Lee
- Subjects
Male ,0301 basic medicine ,medicine.medical_treatment ,Acute Lung Injury ,Anti-Inflammatory Agents ,02 engineering and technology ,Lung injury ,Resveratrol ,Pharmacology ,Transfection ,Micelle ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Drug Delivery Systems ,Administration, Inhalation ,parasitic diseases ,Polyamines ,polycyclic compounds ,medicine ,Animals ,Polyethyleneimine ,General Materials Science ,Lung ,Cells, Cultured ,Micelles ,Mice, Inbred BALB C ,Inhalation ,Gene Transfer Techniques ,technology, industry, and agriculture ,Epithelial Cells ,021001 nanoscience & nanotechnology ,Rats ,Cholesterol ,RAW 264.7 Cells ,030104 developmental biology ,Cytokine ,chemistry ,Lipofectamine ,Critical micelle concentration ,embryonic structures ,lipids (amino acids, peptides, and proteins) ,0210 nano-technology ,Heme Oxygenase-1 - Abstract
Acute lung injury (ALI) is a lung inflammatory disease for which pulmonary delivery of drug and gene could be a useful strategy. In this study, cholesterol-conjugated polyamidoamine (PAM-Chol) was synthesized and characterized as a carrier for combined delivery of anti-inflammatory gene and drug into the lungs by inhalation. The PAM-Chol formed self-assembled micelles in an aqueous solution with a critical micelle concentration of 0.22 mg ml-1. An in vitro transfection assay to L2 lung epithelial cells showed that the PAM-Chol micelle had higher transfection efficiency than lipofectamine and polyethylenimine (25 kDa, PEI25k). As the anti-inflammatory drug, resveratrol was loaded into the cores of the PAM-Chol micelles using the oil-in-water emulsion/solvent evaporation method. In lipopolysaccharide (LPS)-activated macrophage cells, resveratrol-loaded PAM-Chol (PAM-Chol/Res) reduced pro-inflammatory cytokines, confirming the anti-inflammatory effects of resveratrol. In in vitro transfection assays to L2 cells, the PAM-Chol/Res micelles had transfection efficiency similar to that of PAM-Chol. The delivery of resveratrol or the heme oxygenase-1 gene (pHO-1) by inhalation was evaluated in an ALI animal model. Resveratrol delivery using the PAM-Chol/Res micelles inhibited the nuclear translocation of nuclear factor-κB (NF-κB) and reduced pro-inflammatory cytokines in the lungs. pHO-1 delivery using PAM-Chol induced HO-1 expression and reduced pro-inflammatory cytokines. However, the highest anti-inflammatory effects were obtained with combined delivery of pHO-1 and resveratrol using the pHO-1/PAM-Chol/Res complex, as demonstrated in cytokine assays and immunohistochemical studies. Therefore, the PAM-Chol micelle is an efficient carrier of resveratrol and pHO-1 into the lungs and could be useful for the treatment of ALI by inhalation.
- Published
- 2018
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