生物互換性ポリマーナノ粒子は,生物学的に関連する過酸化水素レベルに対応して,荷物を分解し,放出します
Caroline de Gracia Lux1, Shivanjali Joshi-Barr, Trung Nguyen
1Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of NanoEngineering, University of California at San Diego, La Jolla, California 92093, United States.
Journal of the American Chemical Society
|September 6, 2012
まとめ
新しい生物互換性ポリマーは,炎症のマーカーである過酸化水素に反応して薬物を分解し,放出します. このブレークスルーにより,新しいH(2) O(2) 感受性ナノ粒子を使用して,病気の組織に標的を絞った薬物投与が可能になりました.
科学分野:
- バイオマテリアル科学 バイオマテリアル科学
- ポリマー化学のポリマー化学について
- 薬物の配送システムです.
背景:
- 酸化ストレスは,過酸化水素 (H(2) O(2)) の蓄積によって特徴づけられ,炎症した組織と健康な組織を区別する.
- 病気の組織への標的の薬物投与は,刺激反応システムによって強化される可能性があります.
- 既存のポリマー製薬投与システムは,生物学的に重要なH2O2濃度 (50~100μM) に対する感受性が欠けている.
研究 の 目的:
- 低濃度の過酸化水素に敏感な新しい生物互換性ポリマーカプセルを開発する.
- H(2) O(2) 誘発分解と貨物の放出を,標的型薬物投与アプリケーションのために設計する.
- 酸化ストレスへの反応として,治療用ペイロードの放出におけるこれらのポリマーの性能を調査する.
主な方法:
- ボロンエステル結合の2つの生物互換性ポリマーの合成,ポリマーの骨格との結合が異なる (直接対エーテル結合).
- 核磁共振 (NMR) とゲル浸透クロマトグラフィ (GPC) を用いて,ポリマーの安定性と分解運動の特徴づけ.
- これらのポリマーからナノ粒子を作製し,H(2) O(2) 誘発の貨物放出を評価し,活性化中性粒子の性能を評価する.
主要な成果:
- 両ポリマー構造は,水溶液における安定性と,H(2) O(2) に曝露したときに,ボロンエステル分裂と,その後のキノンメチド再配置による分解が示された.
- エーテル結合を特徴とするポリマー2は,ポリマー1と比較して,骨幹の劣化が著しく速く示された.
- ポリマー2のナノ粒子は,ポリマー1の26時間と比較して,1mM H(2) O(2) で10時間以内に完全なレポーター染料の放出を達成し,生物学的に関連するH(2) O(2) レベルでの選択的な放出を示しました.
- ポリマー2ナノ粒子は,活性化中性粒子のインキュベーション時に放出が2倍に増加することを示し,標的反応性を示しました.
結論:
- バイオコンパティブルな新しいポリマーカプセルが開発され,生物学的関連性の過酸化水素濃度に対応して,荷物を分解して放出します.
- エーテル結合ポリマー (ポリマー2) は,より優れたH2O2誘発分解プロファイルを提供し,効率的かつ選択的な薬物放出を可能にします.
- これらのH(2) O(2) 感受性ポリマーは,安全な副産物へと分解する高度な標的型薬物投与システムのための有望なプラットフォームを表しています.
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