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KAKEN_25670081seika.pdf
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:1.3 MB
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生体内動態の時空間制御による機能的核酸デリバリーシステムの創製
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セイタイナイ ドウタイ ノ ジクウカン セイギョ ニ ヨル キノウテキ カクサン デリバリー システム ノ ソウセイ
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Seitainai dotai no jikukan seigyo ni yoru kinoteki kakusan deribari shisutemu no sosei
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Efficient nucleic acid delivery system by spatiotemporal control of the pharmacokinetics
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金澤, 秀子
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カナザワ, ヒデコ
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Kanazawa, Hideko
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慶應義塾大学・薬学部・教授
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Research team head
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科研費研究者番号 : 10240996
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2015
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科学研究費補助金研究成果報告書
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2014
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表面に温度応答性高分子ポリ-N-イソプロピルアクリルアミド(PNIPAAm)共重合体を修飾したカチオン性リポソームを作製した。リポソーム表面の固定水層厚(FALT)を測定し, 細胞取り込み効率について評価した結果, PNIPAAmが親水性となる転移温度LCST以下ではPEG修飾リポソームと同様に表面に水和層が形成され, 血清タンパクとの相互作用を回避でき, 血中安定性が高くなる。一方, LCST以上ではPNIPAAmが脱水和して疎水性となるためFALTが小さくなり, 細胞親和性が高くなり細胞取り込み効率が向上した。毒性も少なく遺伝子導入への応用も可能であった。
We prepared poly (N-isopropylacrylamide-co-N, N-dimethylaminopropyl acrylamide) (PNIPAAm-co-DMAPAAm)-modified liposomes and their temperature-dependent behaviors were investigated. We examined the fixed aqueous layer thickness (FALT) of polymer-modified liposome, and elucidated the connection relationship between physical character and biological properties of these liposomes. Above the lower critical solution temperature (LCST) of the copolymers, the FALT of the liposomes was decreased and the enhanced cellular uptake of the liposomes was observed. The surface properties and cellular uptake of these liposomes can be controlled in a temperature-dependent manner.
In this study, we elucidated that the value of the FALT around the (PNIPAAm-co-DMAPAAm)-modified liposome can be tuned by a changing of temperature and correlates with the cellular uptake. The temperature-sensitive liposome will be an efficacious carrier for the delivery of drugs and nucleic acids.
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研究種目 : 挑戦的萌芽研究
研究期間 : 2013～2014
課題番号 : 25670081
研究分野 : 物理薬剤学, ドラッグデリバリーシステム
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