Abstract:
PURPOSE:A plasmid-based gene expression system was complexed with protective, interactive, and non-condensing (PINC) polymer system and administered with Medi-Jector, a needle-free injection device (NFID), to achieve high and sustained levels of antigen-specific antibodies in blood circulation. METHODS:Human growth hormone (hGH) or bacterial beta-galactosidase gene expression plasmids driven by a cytomegalovirus (CMV) promoter were formulated in saline or complexed with a PINC polymer, polyvinylpyrrolidone (PVP), and intramuscularly or subcutaneously administered into dogs and pigs using a 22-gauge needle or a NFID. The hGH-specific IgG titers in serum were measured by an ELISA. Beta-galactosidase expression was measured in injected muscles by an enzymatic assay or immunohistochemistry. The effect of NFID on DNA stability and topology was assessed by gel electrophoresis. RESULTS:Intramuscular (i.m.) or subcutaneous (s.c.) injection of a hGH expression plasmid pCMV-hGH (0.05-0.5 mg/kg) in dogs and pigs elicited antigen-specific IgG antibody titers to expressed hGH. With both routes of injection, pDNA delivery by a NFID was superior to pDNA injection by needle. The magnitude of hGH-specific IgG titers with NFID was 15-20-fold higher than needle injection when pDNA was complexed with PVP, and only 3-4-fold higher with pDNA in saline. The transfection efficiency in the injected muscle, as measured by beta-galactosidase expression, following i.m. injection of pCMV-betagalactosidase/PVP, was not significantly different between needle and NFID-injected groups. CONCLUSIONS:These data demonstrate that the combination of pDNA/ PVP complexes and a NFID act synergistically to achieve high and sustained levels of antigen-specific IgG response to expressed antigen. This gene delivery approach may offer advantage over needle injection of naked DNA for the development of genetic vaccines.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Anwer K,Earle KA,Shi M,Wang J,Mumper RJ,Proctor B,Jansa K,Ledebur HC,Davis S,Eaglstein W,Rolland APdoi
10.1023/a:1018834305079subject
Has Abstractpub_date
1999-06-01 00:00:00pages
889-95issue
6eissn
0724-8741issn
1573-904Xjournal_volume
16pub_type
杂志文章abstract:PURPOSE:To study the reaction of artelinic acid with chemical model systems of cytochrome P-450 as a means of obtaining authentic samples of the putative metabolites necessary for identification of the mammalian metabolites of artelinic acid. METHODS:Artelinic acid was reacted with different organic complexes of iron(...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012185124972
更新日期:1997-10-01 00:00:00
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018912100826
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journal_title:Pharmaceutical research
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011087012826
更新日期:2001-01-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:1993-01-01 00:00:00
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journal_title:Pharmaceutical research
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doi:10.1007/s11095-021-02991-4
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015842926345
更新日期:1991-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016091915733
更新日期:1996-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
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更新日期:1992-07-01 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11095-004-9019-x
更新日期:2005-01-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1011902625609
更新日期:1999-04-01 00:00:00
abstract::Losartan, an antihypertensive agent in clinical development, was found to exist in two enantiotropic polymorphic forms, a low-temperature stable form (Form I) and a high-temperature stable form (Form II), the temperatures at which they are stable being related to the transition temperature. X-ray powder diffraction pa...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1018973530443
更新日期:1993-06-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2570-2
更新日期:2019-02-22 00:00:00
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pub_type: 杂志文章
doi:10.1007/s11095-005-6947-z
更新日期:2005-10-01 00:00:00
abstract::Lidocaine was administered to healthy volunteers at different sites in the rectum. Unchanged drug and monoethylglycinexylidide (MEGX) concentrations were measured in plasma with a newly developed gas chromatographic method. Lidocaine was given rectally by means of an osmotic system (Osmet(®)) which delivered 25 mg/h a...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/A:1016380104424
更新日期:1984-05-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-005-5276-6
更新日期:2005-08-01 00:00:00
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journal_title:Pharmaceutical research
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更新日期:2013-09-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-012-0855-9
更新日期:2013-01-01 00:00:00
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journal_title:Pharmaceutical research
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doi:10.1023/b:pham.0000045247.09724.26
更新日期:2004-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-014-1600-3
更新日期:2015-06-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1010923924844
更新日期:2001-07-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1015807913934
更新日期:1991-10-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-019-2709-1
更新日期:2019-12-10 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-007-9331-3
更新日期:2008-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016479305603
更新日期:1987-04-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1012058323754
更新日期:1997-03-01 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1007/s11095-018-2378-5
更新日期:2018-03-19 00:00:00
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journal_title:Pharmaceutical research
pub_type: 杂志文章,评审
doi:10.1007/s11095-012-0711-y
更新日期:2012-05-01 00:00:00
abstract::Various diesters of 9-[(1,3-dihydroxy-2-propoxy)-methyl]guanine (DHPG) were screened in order to identify a derivative with improved oral absorption. The solubilities and dissolution rates decreased with increasing chain length and branching of the ester group. However, the dipropionate ester showed an anomalously fas...
journal_title:Pharmaceutical research
pub_type: 杂志文章
doi:10.1023/a:1016462801968
更新日期:1987-04-01 00:00:00