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

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

Nanoscale

Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Republic of Korea.

Published: May 2018

AI Article Synopsis

  • Acute lung injury (ALI) can potentially be treated using a new delivery system that combines an anti-inflammatory gene and drug, specifically through the creation of cholesterol-conjugated polyamidoamine (PAM-Chol) micelles.
  • * The PAM-Chol micelles were shown to have better transfection efficiency compared to other traditional carriers and effectively delivered resveratrol, an anti-inflammatory drug, to reduce inflammation in lung cells.
  • * When tested in an animal model of ALI, the combination of the anti-inflammatory gene (pHO-1) and resveratrol using PAM-Chol micelles resulted in the most significant reduction of inflammatory cytokines, suggesting that this method could be an effective treatment strategy for ALI.*

Article 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.

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Source
http://dx.doi.org/10.1039/c8nr00427gDOI Listing

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