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Carrageenan polyplexes as a non vira...

Georgousis, Vivian C.

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Carrageenan polyplexes as a non viral gene delivery system.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Carrageenan polyplexes as a non viral gene delivery system./
作者:	Georgousis, Vivian C.
面頁冊數:	107 p.
附註:	Source: Dissertation Abstracts International, Volume: 67-09, Section: B, page: 5086.
Contained By:	Dissertation Abstracts International67-09B.
標題:	Chemistry, Pharmaceutical. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3233770
ISBN:	9780542880711

Carrageenan polyplexes as a non viral gene delivery system.
Georgousis, Vivian C.

Carrageenan polyplexes as a non viral gene delivery system. - 107 p.

Source: Dissertation Abstracts International, Volume: 67-09, Section: B, page: 5086.

Thesis (Ph.D.)--Long Island University, The Brooklyn Center, 2006.

The use of nonviral, gene therapy for local delivery to the intestinal epithelium holds significant treatment potential. The objective of this investigation was to explore the feasibility of developing a solid dosage form of plasmid DNA (pDNA) that was stable in the gastrointestinal media and shown transfection competency. kappa-carrageenan was selected as a nonviral vector due to its demonstrated in-vitro mucoadhesive properties.

ISBN: 9780542880711Subjects--Topical Terms:

550957
Chemistry, Pharmaceutical.

Carrageenan polyplexes as a non viral gene delivery system.
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500 $a Source: Dissertation Abstracts International, Volume: 67-09, Section: B, page: 5086.
500 $a Adviser: Michalakis Savva.
502 $a Thesis (Ph.D.)--Long Island University, The Brooklyn Center, 2006.
520 $a The use of nonviral, gene therapy for local delivery to the intestinal epithelium holds significant treatment potential. The objective of this investigation was to explore the feasibility of developing a solid dosage form of plasmid DNA (pDNA) that was stable in the gastrointestinal media and shown transfection competency. kappa-carrageenan was selected as a nonviral vector due to its demonstrated in-vitro mucoadhesive properties.
520 $a Plasmid DNA was propagated in DH5alpha competent E. coli cells at high yields using standard protocols. Formulation trials were executed in methanol-water solvent mixtures to determine the amount of calcium chloride required to efficiently precipitate DNA on to kappa-carrageenan. Evidence regarding the conformation change of DNA due to direct complexation with calcium and partial dehydration due to solvent effects was demonstrated using FTIR. The resultant powder prepared from the formulation process was rapidly hydrated and released DNA without significant change to its secondary structure.
520 $a Formulated polylipoplexes demonstrated decreased stability in gastric media. Compacted DNA tablets were coated with HPMCP, an acid insoluble polymer. An absence of DNA release in simulated gastric media for up to 1 hour was demonstrated followed by release of DNA in simulated intestinal media. Protection from endonucleolytic degradation was studied. The findings demonstrated the need for an excess of cationic lipid to protect DNA from degradation due to the anionic nature of kappa-carrageenan. Based on the data, evidence of competition between polymer and plasmid for lipid association yielding incomplete condensation and reduced endonucleolytic protection of DNA, is postulated.
520 $a The transfection efficiency of the formulation was studied. The results show that all formulations containing kappa-carrageenan showed decreased activity when compared to reference cationic lipoplexes containing equal amounts of calcium chloride.
520 $a The experimental findings suggest that the use of kappa-carrageenan may not be suitable to effectively stabilize or successively deliver DNA to the intestinal epithelium. However, its use for delivery of smaller molecular weight nucleic acid moieties, including oligonucleotides and small, interfering RNAs (siRNA), may still hold promise.
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