Dexamethasone-loaded peptide micelles for delivery of the heme oxygenase-1 gene to ischemic brain
The R3V6 peptides, which are composed of a 3-arginine block and a 6-valine block, formed self-assembled micelles in aqueous solution. Dye quenching assays showed that a hydrophobic fluorescent dye, 5-dodecanoylaminofluorescein (DAF), interacted with and was loaded into the hydrophobic core of the mi...
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| Published in: | Journal of controlled release Vol. 158; no. 1; pp. 131 - 138 |
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28-02-2012
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| Abstract | The R3V6 peptides, which are composed of a 3-arginine block and a 6-valine block, formed self-assembled micelles in aqueous solution. Dye quenching assays showed that a hydrophobic fluorescent dye, 5-dodecanoylaminofluorescein (DAF), interacted with and was loaded into the hydrophobic core of the micelles. In this study, dexamethasone-loaded R3V6 peptide micelles (R3V6-Dexa) were evaluated as a gene carrier. R3V6-Dexa had higher gene delivery efficiency in human embryonic kidney 293 cells compared to those of the R3V6 peptides and poly-l-lysine (PLL). Dexamethasone might stabilize the micelle structure of the R3V6 peptides by forming strong hydrophobic cores and enhanced the transfection efficiency. Furthermore, R3V6-Dexa reduced the expression of an inflammatory cytokine, interleukin-6 (IL-6), more efficiently in lipopolysaccharide (LPS)-induced Raw264.7 cells than did dexamethasone, suggesting that R3V6-Dexa is also a useful carrier for dexamethasone delivery. A focal brain ischemia-reperfusion model was produced by middle cerebral artery occlusion (MCAO). A heme oxygenase-1 (HO-1) expression plasmid DNA, pSV-HO-1, was delivered into the brain using R3V6-Dexa as a carrier. The pSV-HO-1/R3V6-Dexa complex was injected into the brain 1hr prior to MCAO. Twenty-four hours later, the HO-1 expression of the pSV-HO-1/R3V6-Dexa injection group was higher than those of the MCAO control, pβ-Luc/R3V6-Dexa, and pSV-HO-1/PEI25k injection groups. In addition, the infarct size was reduced due to the delivery of pSV-HO-1/R3V6-Dexa complex. Therefore, R3V6-Dexa may be a useful carrier for HO-1 gene delivery and stroke gene therapy.
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| AbstractList | The R3V6 peptides, which are composed of a 3-arginine block and a 6-valine block, formed self-assembled micelles in aqueous solution. Dye quenching assays showed that a hydrophobic fluorescent dye, 5-dodecanoylaminofluorescein (DAF), interacted with and was loaded into the hydrophobic core of the micelles. In this study, dexamethasone-loaded R3V6 peptide micelles (R3V6-Dexa) were evaluated as a gene carrier. R3V6-Dexa had higher gene delivery efficiency in human embryonic kidney 293 cells compared to those of the R3V6 peptides and poly-L-lysine (PLL). Dexamethasone might stabilize the micelle structure of the R3V6 peptides by forming strong hydrophobic cores and enhanced the transfection efficiency. Furthermore, R3V6-Dexa reduced the expression of an inflammatory cytokine, interleukin-6 (IL-6), more efficiently in lipopolysaccharide (LPS)-induced Raw264.7 cells than did dexamethasone, suggesting that R3V6-Dexa is also a useful carrier for dexamethasone delivery. A focal brain ischemia-reperfusion model was produced by middle cerebral artery occlusion (MCAO). A heme oxygenase-1 (HO-1) expression plasmid DNA, pSV-HO-1, was delivered into the brain using R3V6-Dexa as a carrier. The pSV-HO-1/R3V6-Dexa complex was injected into the brain 1hr prior to MCAO. Twenty-four hours later, the HO-1 expression of the pSV-HO-1/R3V6-Dexa injection group was higher than those of the MCAO control, pβ-Luc/R3V6-Dexa, and pSV-HO-1/PEI25k injection groups. In addition, the infarct size was reduced due to the delivery of pSV-HO-1/R3V6-Dexa complex. Therefore, R3V6-Dexa may be a useful carrier for HO-1 gene delivery and stroke gene therapy. The R3V6 peptides, which are composed of a 3-arginine block and a 6-valine block, formed self-assembled micelles in aqueous solution. Dye quenching assays showed that a hydrophobic fluorescent dye, 5-dodecanoylaminofluorescein (DAF), interacted with and was loaded into the hydrophobic core of the micelles. In this study, dexamethasone-loaded R3V6 peptide micelles (R3V6-Dexa) were evaluated as a gene carrier. R3V6-Dexa had higher gene delivery efficiency in human embryonic kidney 293 cells compared to those of the R3V6 peptides and poly-l-lysine (PLL). Dexamethasone might stabilize the micelle structure of the R3V6 peptides by forming strong hydrophobic cores and enhanced the transfection efficiency. Furthermore, R3V6-Dexa reduced the expression of an inflammatory cytokine, interleukin-6 (IL-6), more efficiently in lipopolysaccharide (LPS)-induced Raw264.7 cells than did dexamethasone, suggesting that R3V6-Dexa is also a useful carrier for dexamethasone delivery. A focal brain ischemia-reperfusion model was produced by middle cerebral artery occlusion (MCAO). A heme oxygenase-1 (HO-1) expression plasmid DNA, pSV-HO-1, was delivered into the brain using R3V6-Dexa as a carrier. The pSV-HO-1/R3V6-Dexa complex was injected into the brain 1hr prior to MCAO. Twenty-four hours later, the HO-1 expression of the pSV-HO-1/R3V6-Dexa injection group was higher than those of the MCAO control, pβ-Luc/R3V6-Dexa, and pSV-HO-1/PEI25k injection groups. In addition, the infarct size was reduced due to the delivery of pSV-HO-1/R3V6-Dexa complex. Therefore, R3V6-Dexa may be a useful carrier for HO-1 gene delivery and stroke gene therapy. [Display omitted] |
| Author | Ryu, Jae Hwan Lee, Jiyoung Kim, Jinyoung Park, Ji Hwan Hyun, Hyesun Kim, Hyun Ah Lee, Minhyung |
| Author_xml | – sequence: 1 givenname: Jiyoung surname: Lee fullname: Lee, Jiyoung organization: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea – sequence: 2 givenname: Hyesun surname: Hyun fullname: Hyun, Hyesun organization: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea – sequence: 3 givenname: Jinyoung surname: Kim fullname: Kim, Jinyoung organization: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea – sequence: 4 givenname: Jae Hwan surname: Ryu fullname: Ryu, Jae Hwan organization: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea – sequence: 5 givenname: Hyun Ah surname: Kim fullname: Kim, Hyun Ah organization: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea – sequence: 6 givenname: Ji Hwan surname: Park fullname: Park, Ji Hwan organization: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea – sequence: 7 givenname: Minhyung surname: Lee fullname: Lee, Minhyung email: minhyung@hanyang.ac.kr organization: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea |
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| Copyright | 2011 Elsevier B.V. 2015 INIST-CNRS Copyright © 2011 Elsevier B.V. All rights reserved. |
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| Keywords | Micelle Gene delivery Stroke Gene therapy Peptide Peptides Cardiovascular disease Encephalon Vascular disease Gene Ischemia Genetics Cerebrovascular disease Corticosteroid Nervous system diseases Dexamethasone Pharmaceutical technology Enzyme Steroid hormone Antiinflammatory agent Heme oxygenase (decyclizing) Cerebral disorder Genetic transfer Central nervous system disease Oxidoreductases |
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| SubjectTerms | Animals aqueous solutions Biological and medical sciences brain Brain - metabolism Brain Ischemia - genetics Brain Ischemia - metabolism Cell Line Cell Line, Tumor dexamethasone Dexamethasone - administration & dosage Disease Models, Animal fluorescence Gene delivery Gene therapy Gene Transfer Techniques General pharmacology genes Genetic Therapy HEK293 Cells heme oxygenase (biliverdin-producing) Heme Oxygenase-1 - administration & dosage Heme Oxygenase-1 - genetics Heme Oxygenase-1 - pharmacokinetics Humans hydrophobicity Immunosuppressive Agents - administration & dosage infarction interleukin-6 Interleukin-6 - metabolism kidneys lipopolysaccharides Male Medical sciences Mice Micelle Micelles Oligopeptides - administration & dosage Peptide peptides Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments plasmids Rats Rats, Sprague-Dawley Stroke transfection |
| Title | Dexamethasone-loaded peptide micelles for delivery of the heme oxygenase-1 gene to ischemic brain |
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