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Micellar nanocontainer polymer, pluronic blocker co‐polymer, delivers locally‐confined VEGF siRNA to the cervix of pregnant rat
Author(s) -
Mowa Chishimba Nathan,
Li T,
Folkesson H,
Lopez M,
Jesmin S,
Usip S,
Papka R,
Smith D
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a662-a
Subject(s) - cervix , small interfering rna , chemistry , poloxamer , vegf receptors , copolymer , lipofectamine , pharmacology , microbiology and biotechnology , medicine , polymer , rna , cancer research , biology , biochemistry , cancer , gene , organic chemistry , vector (molecular biology) , recombinant dna
Because VEGF maintains the “life‐line” of fetuses, by ensuring a viable vasculature, systemic administration of VEGF agents is fatal to fetuses and presents a challenge for studying VEGF’s role in cervical ripening. Thus, it is important to develop effective, safe, membrane permeable, time‐released, sustainable and locally confined delivery systems. Here, we use a micellar nanocontainer polymer, pluronic blocker copolymer (nonionic block copolymer surfactant) that meets these conditions. 40 ug of VEGF siRNA dissolved in Lipofectamine and pluronic gel, were intravaginally delivered on day 17 and 19 of pregnancy, and rats killed on day 20 of pregnancy. The effectiveness of the method was analyzed by examining the paleness of treated cervix relative to control, and by a genome‐wide screen of genes downstream of VEGF using DNA microarray and VEGF mRNA levels. VEGF siRNA down regulated 50% of local VEGF, based on densitometric analysis of RT‐PCR gel. The effect of VEGF siRNA was also evident by the paleness of the cervix in treated compared to untreated rats, interpreted as an indication of less vascularization. We conclude that pluronic gel is an effective carrier for VEGF agents, such as siRNA, into the cervix. Support: Appalachian St Univ & NEOUCOM grants.