Combinational therapy of ischemic brain stroke by delivery of heme oxygenase-1 gene and dexamethasone

Hyun, Hyesun; Lee, Ji-Young; Hwang, Do Won; Kim, Soonhag; Cha, Dong‐Hyun; Choi, Joon Sig; Lee, Ja-Kyeong; Lee, Minhyung

doi:10.1016/j.biomaterials.2010.08.116

Cited by 42 publications

(26 citation statements)

References 31 publications

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“…The anti-inflammatory effect of dexamethasone is beneficial to decrease the inflammatory reaction in the ischemic brain (10). In addition to the antiinflammatory effect, PAMAM-Dexa had high transfection efficiency and low cytotoxicity to neuron cells compared with other polymeric carriers.…”

Section: Characterization Of Pamam G2-dexamentioning

confidence: 93%

“…The transfection efficiency of PEI-Dexa was comparable to that of high-molecular weight PEI (25 k, PEI25k). Furthermore, the dexamethasone in PEI-Dexa has an anti-inflammatory effect (10,14,15), indicating that PEI-Dexa might be an anti-inflammatory drug as well as a gene carrier. To enhance the anti-inflammatory effect, dexamethasone was also conjugated to PAMAM G2 (16,17), since PAMAM is reported to have an anti-inflammatory effect by reducing proinflammatory cytokine levels (18).…”

Section: Introductionmentioning

confidence: 97%

“…HO-1 induces oxidative cleavage of the porphyrin ring to generate biliverdin IXα, heme iron, and carbon monoxide (7). Previous studies showed that HO-1 gene delivery reduced the infarct volume and levels of proinflammatory cytokines (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 97%

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Delivery of Hypoxia-Inducible Heme Oxygenase-1 Gene for Site-Specific Gene Therapy in the Ischemic Stroke Animal Model

Choi

Rhim

et al. 2016

Pharm Res

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Section: Characterization Of Pamam G2-dexamentioning

confidence: 93%

Section: Introductionmentioning

confidence: 97%

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Delivery of Hypoxia-Inducible Heme Oxygenase-1 Gene for Site-Specific Gene Therapy in the Ischemic Stroke Animal Model

Choi

Rhim

et al. 2016

Pharm Res

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“…Therefore, the combination delivery of the HO‐1 gene and dexamethasone may have an additive effect on reduction of infarction in the ischemic brain. In our previous report, dexamethasone and the HO‐1 gene were co‐delivered into the brain using PEI‐Dexa, resulting in reduction of infarction volume . In the current study, we evaluated PAMAM G2‐Dexa as an HO‐1 gene carrier for the treatment of ischemic stroke.…”

Section: Introductionmentioning

confidence: 97%

Dexamethasone‐Conjugated Polyamidoamine Dendrimer for Delivery of the Heme Oxygenase‐1 Gene into the Ischemic Brain

Jeon

Choi

et al. 2015

Macromolecular Bioscience

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Heme oxygenase-1 (HO-1) has anti-apoptotic and anti-inflammatory effects. In this study, the HO-1 gene was delivered into the brain using dexamethasone-conjugated polyamidoamine generation 2 (PAMAM G2-Dexa) for the treatment of ischemic stroke. PAMAM G2-Dexa formed stable complexes with plasmid DNA (pDNA). The pDNA delivery efficiency of PAMAM G2-Dexa was higher than that of polyethylenimine (PEI25k, 25 kDa), dexamethasone-conjugated PEI (PEI-Dexa), and PAMAM G2 in Neuro2A cells. Therapeutic effect of PAMAM G2-Dexa/pHO-1 complexes was evaluated in a stroke animal model. PAMAM G2-Dexa delivered pHO-1 more efficiently into the ischemic brain than PEI25k and PEI-Dexa with higher therapeutic effect. Therefore, PAMAM G2-Dexa/pHO-1 complexes may be useful for ischemic stroke gene therapy.

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“…It was previously shown that hydrophobic drugs such as dexamethasone, curcumin, and BCNU could be loaded within the cores of R3V6 peptide micelles. 8,9 In vitro studies showed that BCNU-loaded R3V6 (R3V6-BCNU) more efficiently delivered siRNA or plasmid DNA (pDNA) than did empty R3V6 micelles. 10 Furthermore, the R3V6-BCNU/pDNA complex were more toxic to the cancer cells than was the mixture of BCNU and pDNA.…”

Section: Introductionmentioning

confidence: 99%

Peptide Micelles for Anti-cancer Drug Delivery in an Intracranial Glioblastoma Animal Model

Yi¹,

Lee²

2014

Bulletin of the Korean Chemical Society

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Bis-chloroethylnitrosourea (BCNU) is currently used as an anti-cancer drug for glioblastoma therapy. In this study, BCNU was loaded into the hydrophobic cores of R3V6 amphiphilic peptide micelles for efficient delivery into brain tumors. The scanning electron microscope (SEM) study showed that the BCNU-loaded R3V6 peptide micelles (R3V6-BCNU) formed spherical micelles. MTT assay showed that R3V6-BCNU more efficiently induced cell death in C6 glioblastoma cells than did BCNU. In the Annexin V assay, R3V6-BCNU more efficiently induced apoptosis than did BCNU alone. Furthermore, the results showed that R3V6 was not toxic to cells. The positive charges of the R3V6 peptide micelles may facilitate the interaction between R3V6-BCNU and the cellular membrane, resulting in an increase in cellular uptake of BCNU. In vivo evaluation with an intracranial glioblastoma rat model showed that R3V6-BCNU more effectively reduced tumor size than BCNU alone. The results suggest that R3V6 peptide micelles may be an efficient carrier of BCNU for glioblastoma therapy.

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Combinational therapy of ischemic brain stroke by delivery of heme oxygenase-1 gene and dexamethasone

Cited by 42 publications

References 31 publications

Delivery of Hypoxia-Inducible Heme Oxygenase-1 Gene for Site-Specific Gene Therapy in the Ischemic Stroke Animal Model

Delivery of Hypoxia-Inducible Heme Oxygenase-1 Gene for Site-Specific Gene Therapy in the Ischemic Stroke Animal Model

Dexamethasone‐Conjugated Polyamidoamine Dendrimer for Delivery of the Heme Oxygenase‐1 Gene into the Ischemic Brain

Peptide Micelles for Anti-cancer Drug Delivery in an Intracranial Glioblastoma Animal Model

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