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Self-assembled polymeric micelles for combined delivery of anti-inflammatory gene and drug to the lungs by inhalation

Title
Self-assembled polymeric micelles for combined delivery of anti-inflammatory gene and drug to the lungs by inhalation
Author
이민형
Keywords
RESPIRATORY-DISTRESS-SYNDROME; HEME OXYGENASE-1 GENE; POLYAMIDOAMINE DENDRIMERS; INFLAMMATORY MEDIATORS; ISCHEMIC BRAIN; PLASMID DNA; INJURY; RESVERATROL; DEXAMETHASONE; THERAPY
Issue Date
2018-05
Publisher
ROYAL SOC CHEMISTRY
Citation
NANOSCALE, v. 10, no. 18, page. 8503-8514
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-kappa B (NF-kappa B) 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.
URI
https://pubs.rsc.org/en/content/articlelanding/2018/NR/C8NR00427G#!divAbstracthttps://repository.hanyang.ac.kr/handle/20.500.11754/118674
ISSN
2040-3364; 2040-3372
DOI
10.1039/c8nr00427g
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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