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Synthesis and Characterization of New Cationic Polyphosphazenes as a Non-viral Vector for Gene Delivery

Synthesis and Characterization of New Cationic Polyphosphazenes as a Non-viral Vector for Gene Delivery
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대학원 나노과학부
Polyphosphazene, gene delivery, biodegradable, non-viral vector, cationic polymer;polyplex, zetapotential, duru delivery system, sol-gel, thermosesitivity
이화여자대학교 대학원
Currently, gene delivery systems can be divided into two parts: viral or non-viral vectors. In general, viral vectors as the gene carrier show efficient gene transfer but severe disadvantages are associated, and recently, as an alternative way, cationic lipids and polymers are intensively studied as non-viral carrier systems. Unfortunately, most of non-viral vectors showed relatively lower transfection rate. The aim of this study is to develop a non-viral vector for gene delivery system. Poly(organophosphazenes) are a good candidate as a non-viral vector for gene delivery, because of their biodegradability and versatility in molecular design for desired chemical and physical properties. We have designed and synthesized a new cationic polyphosphazene by stepwise nucleophilic substitutions of hexachlorocyclotriphosphazene with poly(ethylene glycol) as solubilizing group and dilycine as cationic site. A new class of thermosensitive poly(organophosphazene) gels were synthesized by stepwise nucleophilic substitutions of poly(dichlorophosphazene) with methoxy-poly(ethylene glycol) (MPEG) and highly hydrophobic tripeptides such as GlyPheIleEt, GlyPheLeuEt, as side groups and characterized by means of multinuclear (1H, 31P) NMR spectroscopy, gel permeation chromatography, and elemental analysis. Their temperature-dependent sol-gel properties were investigated by viscometer. In an aqueous solution, the poly(organophosphazenes) exhibited four-phase transitions with increasing temperature: a transparent sol, a transparent gel, an opaque gel, and a turbid sol. The gelation properties of the polymer were affected by several factors such as the composition of substituents, the hydrophobicity of the oligopeptides, and the concentration of the polymer solutions. The gelation of the polymer is presumed to be attributed to the hydrophobic interaction between the hydrophobic oligopeptide side groups, which form the physical junction zone in the polymer aqueous solution.
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