Combined delivery of curcumin and the heme oxygenase-1 gene using cholesterol-conjugated polyamidoamine for anti-inflammatory therapy in acute lung injury

Gyeungyun Kim, Chunxian Piao, Jungju Oh, Minhyung Lee

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: Acute lung injury (ALI) is an inflammatory lung disease with a high mortality rate. In this study, combined delivery of the anti-inflammatory compound curcumin and the heme-oxygenase-1 (HO-1) gene using cholesterol-conjugated polyamidoamine was evaluated in a mouse model as a therapeutic option for ALI. Methods: Curcumin was loaded into cholesterol-conjugated polyamidoamine (PamChol) micelles, and curcumin-loaded PamChol (PamChol-Cur) was then complexed with plasmid DNA (pDNA) through charge interactions. The pDNA/PamChol-Cur complex was physically characterized by dynamic light scattering, gel retardation, and heparin competition assay. Gene delivery efficiency was measured by luciferase assay. The HO-1 expression plasmid (pHO-1)/PamChol-Cur complex was administrated into the ALI model via intratracheal injection. The anti-inflammatory effect of the pDNA/PamChol-Cur complex was evaluated by ELISA, immunohistochemistry, and hematoxylin and eosin staining. Results: The pDNA/PamChol-Cur complex had a size of approximately 120 nm with a positive surface charge. The in vitro plasmid DNA (pDNA) delivery efficiency of the pDNA/PamChol-Cur complex into L2 lung epithelial cells was higher than that of pDNA/PamChol. In addition, the curcumin in the pDNA/PamChol-Cur complex inhibited the nuclear translocation of NF-κB, suggesting an anti-inflammatory effect of curcumin. In the ALI animal model, the pHO-1/PamChol-Cur complex delivered the pHO-1 gene more efficiently than pHO-1/PamChol. In addition, the pHO-1/PamChol-Cur complex showed greater anti-inflammatory effects by reducing anti-inflammatory cytokine levels more than delivery of pHO-1/PamChol or PamChol-Cur only. Conclusion: The pHO-1/PamChol-Cur complex had a higher pHO-1 gene-delivery efficiency and greater anti-inflammatory effects than the pHO-1/PamChol complex or PamChol-Cur. Therefore, the combined delivery of curcumin and pHO-1 using PamChol-Cur may be useful for treatment of ALI.

Original languageEnglish
Pages (from-to)165-174
Number of pages10
JournalPhytomedicine
Volume56
DOIs
StatePublished - 2019 Mar 15

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Heme Oxygenase-1
Curcumin
Acute Lung Injury
Anti-Inflammatory Agents
Micelles
Cholesterol
Genes
Plasmids
Therapeutics
DNA
Poly(amidoamine)

Keywords

  • Acute lung injury
  • Curcumin
  • Gene delivery
  • Gene therapy
  • Polymeric micelle

Cite this

@article{d876f42572a147f1a6fac277e4f1c4c4,
title = "Combined delivery of curcumin and the heme oxygenase-1 gene using cholesterol-conjugated polyamidoamine for anti-inflammatory therapy in acute lung injury",
abstract = "Background: Acute lung injury (ALI) is an inflammatory lung disease with a high mortality rate. In this study, combined delivery of the anti-inflammatory compound curcumin and the heme-oxygenase-1 (HO-1) gene using cholesterol-conjugated polyamidoamine was evaluated in a mouse model as a therapeutic option for ALI. Methods: Curcumin was loaded into cholesterol-conjugated polyamidoamine (PamChol) micelles, and curcumin-loaded PamChol (PamChol-Cur) was then complexed with plasmid DNA (pDNA) through charge interactions. The pDNA/PamChol-Cur complex was physically characterized by dynamic light scattering, gel retardation, and heparin competition assay. Gene delivery efficiency was measured by luciferase assay. The HO-1 expression plasmid (pHO-1)/PamChol-Cur complex was administrated into the ALI model via intratracheal injection. The anti-inflammatory effect of the pDNA/PamChol-Cur complex was evaluated by ELISA, immunohistochemistry, and hematoxylin and eosin staining. Results: The pDNA/PamChol-Cur complex had a size of approximately 120 nm with a positive surface charge. The in vitro plasmid DNA (pDNA) delivery efficiency of the pDNA/PamChol-Cur complex into L2 lung epithelial cells was higher than that of pDNA/PamChol. In addition, the curcumin in the pDNA/PamChol-Cur complex inhibited the nuclear translocation of NF-κB, suggesting an anti-inflammatory effect of curcumin. In the ALI animal model, the pHO-1/PamChol-Cur complex delivered the pHO-1 gene more efficiently than pHO-1/PamChol. In addition, the pHO-1/PamChol-Cur complex showed greater anti-inflammatory effects by reducing anti-inflammatory cytokine levels more than delivery of pHO-1/PamChol or PamChol-Cur only. Conclusion: The pHO-1/PamChol-Cur complex had a higher pHO-1 gene-delivery efficiency and greater anti-inflammatory effects than the pHO-1/PamChol complex or PamChol-Cur. Therefore, the combined delivery of curcumin and pHO-1 using PamChol-Cur may be useful for treatment of ALI.",
keywords = "Acute lung injury, Curcumin, Gene delivery, Gene therapy, Polymeric micelle",
author = "Gyeungyun Kim and Chunxian Piao and Jungju Oh and Minhyung Lee",
year = "2019",
month = "3",
day = "15",
doi = "10.1016/j.phymed.2018.09.240",
language = "English",
volume = "56",
pages = "165--174",
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Combined delivery of curcumin and the heme oxygenase-1 gene using cholesterol-conjugated polyamidoamine for anti-inflammatory therapy in acute lung injury. / Kim, Gyeungyun; Piao, Chunxian; Oh, Jungju; Lee, Minhyung.

In: Phytomedicine, Vol. 56, 15.03.2019, p. 165-174.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Combined delivery of curcumin and the heme oxygenase-1 gene using cholesterol-conjugated polyamidoamine for anti-inflammatory therapy in acute lung injury

AU - Kim, Gyeungyun

AU - Piao, Chunxian

AU - Oh, Jungju

AU - Lee, Minhyung

PY - 2019/3/15

Y1 - 2019/3/15

N2 - Background: Acute lung injury (ALI) is an inflammatory lung disease with a high mortality rate. In this study, combined delivery of the anti-inflammatory compound curcumin and the heme-oxygenase-1 (HO-1) gene using cholesterol-conjugated polyamidoamine was evaluated in a mouse model as a therapeutic option for ALI. Methods: Curcumin was loaded into cholesterol-conjugated polyamidoamine (PamChol) micelles, and curcumin-loaded PamChol (PamChol-Cur) was then complexed with plasmid DNA (pDNA) through charge interactions. The pDNA/PamChol-Cur complex was physically characterized by dynamic light scattering, gel retardation, and heparin competition assay. Gene delivery efficiency was measured by luciferase assay. The HO-1 expression plasmid (pHO-1)/PamChol-Cur complex was administrated into the ALI model via intratracheal injection. The anti-inflammatory effect of the pDNA/PamChol-Cur complex was evaluated by ELISA, immunohistochemistry, and hematoxylin and eosin staining. Results: The pDNA/PamChol-Cur complex had a size of approximately 120 nm with a positive surface charge. The in vitro plasmid DNA (pDNA) delivery efficiency of the pDNA/PamChol-Cur complex into L2 lung epithelial cells was higher than that of pDNA/PamChol. In addition, the curcumin in the pDNA/PamChol-Cur complex inhibited the nuclear translocation of NF-κB, suggesting an anti-inflammatory effect of curcumin. In the ALI animal model, the pHO-1/PamChol-Cur complex delivered the pHO-1 gene more efficiently than pHO-1/PamChol. In addition, the pHO-1/PamChol-Cur complex showed greater anti-inflammatory effects by reducing anti-inflammatory cytokine levels more than delivery of pHO-1/PamChol or PamChol-Cur only. Conclusion: The pHO-1/PamChol-Cur complex had a higher pHO-1 gene-delivery efficiency and greater anti-inflammatory effects than the pHO-1/PamChol complex or PamChol-Cur. Therefore, the combined delivery of curcumin and pHO-1 using PamChol-Cur may be useful for treatment of ALI.

AB - Background: Acute lung injury (ALI) is an inflammatory lung disease with a high mortality rate. In this study, combined delivery of the anti-inflammatory compound curcumin and the heme-oxygenase-1 (HO-1) gene using cholesterol-conjugated polyamidoamine was evaluated in a mouse model as a therapeutic option for ALI. Methods: Curcumin was loaded into cholesterol-conjugated polyamidoamine (PamChol) micelles, and curcumin-loaded PamChol (PamChol-Cur) was then complexed with plasmid DNA (pDNA) through charge interactions. The pDNA/PamChol-Cur complex was physically characterized by dynamic light scattering, gel retardation, and heparin competition assay. Gene delivery efficiency was measured by luciferase assay. The HO-1 expression plasmid (pHO-1)/PamChol-Cur complex was administrated into the ALI model via intratracheal injection. The anti-inflammatory effect of the pDNA/PamChol-Cur complex was evaluated by ELISA, immunohistochemistry, and hematoxylin and eosin staining. Results: The pDNA/PamChol-Cur complex had a size of approximately 120 nm with a positive surface charge. The in vitro plasmid DNA (pDNA) delivery efficiency of the pDNA/PamChol-Cur complex into L2 lung epithelial cells was higher than that of pDNA/PamChol. In addition, the curcumin in the pDNA/PamChol-Cur complex inhibited the nuclear translocation of NF-κB, suggesting an anti-inflammatory effect of curcumin. In the ALI animal model, the pHO-1/PamChol-Cur complex delivered the pHO-1 gene more efficiently than pHO-1/PamChol. In addition, the pHO-1/PamChol-Cur complex showed greater anti-inflammatory effects by reducing anti-inflammatory cytokine levels more than delivery of pHO-1/PamChol or PamChol-Cur only. Conclusion: The pHO-1/PamChol-Cur complex had a higher pHO-1 gene-delivery efficiency and greater anti-inflammatory effects than the pHO-1/PamChol complex or PamChol-Cur. Therefore, the combined delivery of curcumin and pHO-1 using PamChol-Cur may be useful for treatment of ALI.

KW - Acute lung injury

KW - Curcumin

KW - Gene delivery

KW - Gene therapy

KW - Polymeric micelle

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U2 - 10.1016/j.phymed.2018.09.240

DO - 10.1016/j.phymed.2018.09.240

M3 - Article

VL - 56

SP - 165

EP - 174

JO - Phytomedicine

JF - Phytomedicine

SN - 0944-7113

ER -