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Synthesis and Characterization of New Thermosensitive Cyclotriphosphazenes and Diblock Copolymers
- Synthesis and Characterization of New Thermosensitive Cyclotriphosphazenes and Diblock Copolymers
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- 대학원 나노과학부
- 이화여자대학교 대학원
- Amphiphilic cyclotriphosphazenes bearing hydrophilic poly(ethylene glycol) and a variety of lipophilic oligopeptide esters as side groups were synthesized and characterized by elemental analysis, 1H and 31P-NMR. These trimeric phosphazenes were found to exhibit a lower critical solution temperature (LCST) around and higher than the body temperature and to form micelles by self-assembly in aqueous solution. Therefore, these cyclotriphosphazenes were evaluated for their applications as new delivery systems for anticancer drugs.
A new class of amphiphilic diblock copolymers were synthesized by conjugating hydrophobic oligopeptides to hydrophilic poly(ethylene glycol) through ether linkage. These diblock copolymers were found to form stable micelles by self- assembly and to exhibit a critical solution temperature (LCST) in a wide range of temperature including body temperature, which is potentially applicable to both systemic and local drug delivery. These amphiphilic copolymers may be applied as drug carriers either for solubilizing or conjugating hydrophobic drugs such as protein and anticancer drugs including paclitaxel and platinum.
In order to overcome disadvantages of conventional platinum drug such as toxic side effects including nephrotoxicity and neurotoxicity, a new class of copolymer-platinum conjugates was synthesized, and their antitumor activity was studied. The oligopeptide esters of the copolymer were functionalyzed by hydrolysis using barium hydroxide or potassium hydroxide, followed by platination with (NH3)(CHA)Pt(SO4) or Pt(CHA)2(NO3)2 to create new tumor?active copolymer-platinum conjugate. These copolymer-Pt(II) conjugates were found to exhibit lower cytotoxicity than cisplatin in vitro. The present conjugates are promising candidates for selective local delivery of platinum anticancer drugs for the treatments of various solid tumors.
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