Tissue distribution and persistence in mice of plasmid DNA encapsulated in a PLGA-based microsphere delivery vehicle

被引:57
作者
Lunsford, L [1 ]
McKeever, U [1 ]
Eckstein, V [1 ]
Hedley, ML [1 ]
机构
[1] Zycos Inc, Cambridge, MA 02138 USA
关键词
antigen presenting cells; biodistribution; microspheres; plasmid DNA; PLGA;
D O I
10.3109/10611860009009208
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Information regarding the distribution and persistence of DNA encapsulated in poly(lactide co-glycolide) microspheres was collected to provide additional information regarding the safety of DNA vaccines and to support the clinical testing of this new delivery system for DNA, Plasmid DNA was encapsulated in poly(lactide co-glycolide) microspheres and the distribution and persistence of plasmid in murine tissues resulting from parenteral administration were examined by a sensitive PCR assay. Encapsulated DNA delivered by intramuscular or subcutaneous injection can be detected for 100 days post-injection and is distributed primarily at the site of injection and the lymphoid organs. Intravenous administration results in more widespread dissemination with long term persistence limited to the lymphoid organs and those of the reticuloendothelial system. Specific cellular uptake of DNA by professional antigen presenting cells (APCs) following injection suggests the utility of microspheres as DNA delivery agents. Distribution and persistence studies support the safety of encapsulated DNA and the specific cellular uptake of DNA by professional APCs following injection suggests the utility of microspheres as DNA delivery agents.
引用
收藏
页码:39 / 50
页数:12
相关论文
共 38 条
[1]  
AKANE A, 1994, J FORENSIC SCI, V39, P362
[2]   DNA vaccination: Transfection and activation of dendritic cells as key events for immunity [J].
Akbari, O ;
Panjwani, N ;
Garcia, S ;
Tascon, R ;
Lowrie, D ;
Stockinger, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (01) :169-177
[3]   PLGA microspheres containing plasmid DNA: Preservation of supercoiled DNA via cryopreparation and carbohydrate stabilization [J].
Ando, S ;
Putnam, D ;
Pack, DW ;
Langer, R .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1999, 88 (01) :126-130
[4]   Antigen presentation by dendritic cells after immunization with DNA encoding a major histocompatibility complex class II-restricted viral epitope [J].
Casares, S ;
Inaba, K ;
Brumeanu, TD ;
Steinman, RM ;
Bona, CA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (09) :1481-1486
[5]   Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles [J].
Chen, SC ;
Jones, DH ;
Fynan, EF ;
Farrar, GH ;
Clegg, JCS ;
Greenberg, HB ;
Herrmann, JE .
JOURNAL OF VIROLOGY, 1998, 72 (07) :5757-5761
[6]   Gene vaccination with naked plasmid DNA: Mechanism of CTL priming [J].
Corr, M ;
Lee, DJ ;
Carson, DA ;
Tighe, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (04) :1555-1560
[7]  
DANKO I, 1994, GENE THER, V1, P114
[8]   Immune-mediated destruction of transfected muscle fibers after direct gene transfer with antigen-expressing plasmid DNA [J].
Davis, HL ;
Millan, CLB ;
Watkins, SC .
GENE THERAPY, 1997, 4 (03) :181-188
[9]   Induction of cytotoxic T lymphocytes by intramuscular immunization with plasmid DNA is facilitated by bone marrow-derived cells [J].
Doe, B ;
Selby, M ;
Barnett, S ;
Baenziger, J ;
Walker, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (16) :8578-8583
[10]   DNA vaccines [J].
Donnelly, JJ ;
Ulmer, JB ;
Shiver, JW ;
Liu, MA .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :617-648