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변향민,박상은,김정목,고정재,오유경 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.3
This study report the encapsulation of plasmid DNA in erythrocyte ghosts. The plasmid DNA was encapsulated into erythrocyte ghosts using three methods; osmotic shock, electroporation in isotonic medium, and electroporation in hypotonic medium. Of three methods, electroporation in hypotonic medium resulted in the highest encapsulation efficiency of plasmid DNA. The morpholohy of erythrocyte ghosts prepared by electroporaion in hypotonic medium was similar to that by osmotic shock alone. The circulation time of plasmid DNA in mice was prolonged by administration in erythrocyte ghost-encapsulated forms. These results indicated the potential of erythrocyte ghosts for biocompative nonviral delivery system of therapeutic genes for hematological diseases.
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혈구세포 수송체로 투여된 트레일 유전자의 혈중 발현 지속 효과
변향민,권경애,신지영,오유경 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.4
Tumor necrosis factor-related apoptosis -inducing ligand (TRAIL) is a recently identified member of the tumor necrosis factor cytokine superfamily. TRAIL has been shown to induce apoptosis in a number of tumor cells whereas cells from most of normal tissues are highly resistant to TRAIL-induced apoptosis. These observations have raised considerable interest in the use of TRAIL in tumor therapy. In this study we report the biodistribution fates and serum expression pattern of plasmid DNA encoding TRAIL (pTRAIL) delivered in erythrocyte ghosts(EG). pTRAIL was loaded into EG by electroporation in a hypotonic medium. The mRNA expression of pTRAIL was prolonged following delivery in EG-encap-sulated forms. EG containing pTRAIL showed significant levels of mRNA expression in the blood over 9 days. The organ expression patterns of pTRAIL delivered via EG, however, did not significantly differ from those of naked pTRAIL, indicating that the expression-enhancing effect of EG containing pTRAIL, was localized to the blood. These results suggest that pTRAIL-loaded EG might be of potential use in the treatment of hematological diseases such as TRAIL-sensitive leukemia.
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골수 유래 기질 줄기세포의 탐식작용 매개성 케모카인 수용체 발현 연구
정영신,변향민,신지영,김정목,정형민,오유경 한국약제학회 2003 Journal of Pharmaceutical Investigation Vol.33 No.4
To design gene delivery systems which can deliver higher amounts of genes into stem cells, we studied the expression of receptors involved in the receptor-mediated endocytosis of bone marrow stromal stem cells. Bone marrow was isolated from ICR mice, and bone marrow stromal stem cells were isolated based on their plastic adherence property. Several cultrure conditions were screened for effective and continuous culture of marrow stromal stem cells. MesenCult medium was finally used to cultivate marrow stromal stem cells in vitro. As candidate receptors, various chemokine receptors were studied. Both bone marrow cells and marrow-derived stromal stem cells showed expression of CC chemokine receptors (CCR) and CXC chemokine receptors (CXCR). Marrow stromal stem cells showed higher expression of CCR5 and CXCR4 chemokine receptors as compared to other types of chemokine receptors. Moreover, though the expression chemokine receptors generally decreased in most chemokine receptors with the cultivation of marrow stromal stem cells, CCR5 and CXCR4 chemokine receptors retained the higher lever of receptor expressions over prolonged periods. These results suggest that the ligands exhibiting specific binding to CCR5 or CXCR4 might be used to modify gene delivery systems for increased level of receptor-mediated gene delivery into stromal stem cells.
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