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Gemini cationic surfactant-based del...

Badea, Ildiko.

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Gemini cationic surfactant-based delivery systems for non-invasive cutaneous gene therapy.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Gemini cationic surfactant-based delivery systems for non-invasive cutaneous gene therapy./
Author:	Badea, Ildiko.
Description:	222 p.
Notes:	Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5681.
Contained By:	Dissertation Abstracts International67-10B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR18174
ISBN:	9780494181744

Gemini cationic surfactant-based delivery systems for non-invasive cutaneous gene therapy.
Badea, Ildiko.

Gemini cationic surfactant-based delivery systems for non-invasive cutaneous gene therapy. - 222 p.

Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5681.

Thesis (Ph.D.)--The University of Saskatchewan (Canada), 2006.

Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. Topical gene therapy involves administration of the genetic material onto the surface of skin and mucosal membranes. Cationic gemini surfactants (m-s-m, where m represents the carbon atoms in the alkyl tail and s represents the carbon atoms in the spacer) are a novel category of delivery agents with especially high potential for polynucleotides. This is due to their structural versatility, ability to bind and condense DNA, and relatively low toxicity.

ISBN: 9780494181744Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Gemini cationic surfactant-based delivery systems for non-invasive cutaneous gene therapy.
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020 $a 9780494181744
035 $a (UMI)AAINR18174
035 $a AAINR18174
040 $a UMI $c UMI
100 1 $a Badea, Ildiko. $3 1296292
245 1 0 $a Gemini cationic surfactant-based delivery systems for non-invasive cutaneous gene therapy.
300 $a 222 p.
500 $a Source: Dissertation Abstracts International, Volume: 67-10, Section: B, page: 5681.
502 $a Thesis (Ph.D.)--The University of Saskatchewan (Canada), 2006.
520 $a Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. Topical gene therapy involves administration of the genetic material onto the surface of skin and mucosal membranes. Cationic gemini surfactants (m-s-m, where m represents the carbon atoms in the alkyl tail and s represents the carbon atoms in the spacer) are a novel category of delivery agents with especially high potential for polynucleotides. This is due to their structural versatility, ability to bind and condense DNA, and relatively low toxicity.
520 $a The objectives were to design, construct and characterize a cationic, non-viral gemini surfactant-based delivery system for an IFN-gamma coding plasmid suitable for cutaneous gene therapy and to evaluate this novel therapeutic approach in a Tsk (tight-skin scleroderma) mouse model to determine its clinical feasibility.
520 $a The delivery systems were characterized by microscopy, dynamic light scattering (DLS), circular dichroism (CD) and small angle X-ray scattering (SAXS). In vitro gene expression was evaluated in PAM 212 keratmocyte culture. The extent of topical delivery of the plasmid using nanoparticle and nanoemulsion formulations was evaluated by measuring IFN-gamma levels in CD1, IFN-gamma-deficient and Tsk mice. The effect of transgene expression on collagen synthesis was evaluated in Tsk animals by real-time PCR.
520 $a The in vitro plasmid-gemini-lipid (PGL) system showed heterogeneous particle size (100-200 nm small particles and 300-600 nm aggregates). Electrostatic interactions between the DNA and PGL systems shifted the negative zeta-potential of the DNA (-47 mV) to positive values (30-50 mV). At the same time, condensation of the DNA, and formation of Psi- DNA was indicated by the increase of the overall negative signal in the CD spectra, due to the flattening of the 290 nm peak and shift of the 260 nm peak into the negative region in a structure-dependent manner. Lipid organization of the DNA-DOPE system, in the absence of gemini surfactants, shows hexagonal structure, while addition of gemim surfactant at +/- charge ratio of 10 caused lamellar phase organization. For short spacers (n=3-6), additional Pn3m cubic phase also appear to be present. (Abstract shortened by UMI.)
590 $a School code: 0780.
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0419
710 2 0 $a The University of Saskatchewan (Canada). $3 1025078
773 0 $t Dissertation Abstracts International $g 67-10B.
790 $a 0780
791 $a Ph.D.
792 $a 2006
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=NR18174