JP2016520567A - 生物学的実体のカプセル化のためのナノスケールコーティング - Google Patents
生物学的実体のカプセル化のためのナノスケールコーティング Download PDFInfo
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Abstract
Description
Si(OCH3)4 + 2 H2O → SiO2 + 4 CH3OH
を含み得る。
下記の実施例は本技術のいくつかの実施形態の実例である。本技術の他の典型的な実施形態は、以下に挙げる実施例の前に、または以下に挙げる実施例の後に提供され得る。
Claims (40)
- 生物活性ペイロード送達デバイスを製造する方法であって、
ポリマー材料と生体物質とを静電力に基づいて結合することにより中間構造を形成すること(ここで、形成された中間構造は正味表面電荷を有する複数の領域を含む);および
形成された中間構造上に生体適合性材料の被覆構造を直接形成して、生体物質を封入することを含み、
前記被覆構造がその中に封入された生体物質の生物活性を保存し、それにより生物活性ペイロード送達デバイスを製造する、前記方法。 - 被覆構造がナノメートル領域のサイズを有するナノ粒子を含む、請求項1に記載の方法。
- 生体物質が、ウイルス、細菌、タンパク質、酵素、プロドラッグ、またはDNAもしくはRNAを含む核酸ベクターの少なくとも1つを含む、請求項1に記載の方法。
- 生体適合性材料がシリカを含む、請求項1に記載の方法。
- 中間構造の形成が、生体物質とポリカチオン性ポリマー材料とを交差反応させて、中間構造の複数の領域に正に荷電した表面を形成することを含む、請求項1に記載の方法。
- ポリカチオン性ポリマー材料がポリ-L-リシンを含む、請求項5に記載の方法。
- 被覆構造の形成が、中間構造の表面上への直接の電荷媒介シリカゾル-ゲル縮合反応を含み、形成された被覆構造が生体物質をカプセル化する外被シリカマトリックスを含む、請求項6に記載の方法。
- さらに、被覆構造の内側に超音波が誘発するキャビテーションの中心を作るための増感剤を加えることを含み、
前記増感剤の添加が被覆構造を形成する前に実施される、請求項1に記載の方法。 - 増感剤がフルオロカーボンナノエマルションを含む、請求項8に記載の方法。
- さらに、生体物質を生体中の標的細胞または組織に送達することを含み、前記送達が、
製造された生物活性ペイロード送達デバイスを体の血管系を通して注入し、その際に、生物活性ペイロード送達デバイスが血管系から標的細胞または組織に血管外遊出すること、
標的細胞または組織を含むまたはそれらに近接する生体の領域に音波エネルギーを適用して、増感剤による被覆構造の破裂および生体物質の標的細胞または組織への放出を引き起こすことを含む、請求項8に記載の方法。 - さらに、被覆構造に封入される中間構造と共に医薬品または治療薬を加えることを含み、
前記医薬品または治療薬の添加が被覆構造を形成する前に実施される、請求項1に記載の方法。 - さらに、生体適合性材料と共に酸化鉄成分または他のナノスケール材料を加えて被覆構造を形成することを含み、
加えられた酸化鉄成分または他のナノスケール材料が被覆構造の画像化を増強する薬剤を提供する、請求項1に記載の方法。 - 被覆構造がその中に封入された生体物質を安定化し、それにより80℃〜-37℃を含む温度における熱安定性を提供する、請求項1に記載の方法。
- さらに、製造された生物活性ペイロード送達デバイスを凍結乾燥または臨界点乾燥することを含み、
その際に、被覆構造が、凍結乾燥または臨界点乾燥された生物活性ペイロード送達デバイス内に封入された生体物質の生物活性を保存する、請求項1に記載の方法。 - さらに、被覆構造の外面を官能基化することを含む、請求項1に記載の方法。
- 官能基化が、ポリエチレングリコール(PEG)を加えて、生物活性ペイロード送達デバイスが配置される生体内での免疫系応答の阻止が可能な二次コーティングを提供することを含む、請求項15に記載の方法。
- 官能基化が、生物活性ペイロード送達デバイスが配置される生体の細胞または組織の特定の領域に選択的に結合可能な標的化リガンドを結合することを含む、請求項15に記載の方法。
- 官能基化が、前記外面に環境感知部分を結合することを含み、前記環境感知部分が、生物活性ペイロード送達デバイスが配置される局所環境における酸化還元反応、低酸素反応、または酸性のpHのうちの少なくとも1つに基づいて化学的に形態を変化させることができる、請求項15に記載の方法。
- さらに、被覆構造を形成する前に、中間構造に標的化部分を結合して、被覆構造からの生体物質の制御放出を可能にすることを含む、請求項1に記載の方法。
- さらに、製造された生物活性ペイロード送達デバイスを流動性媒体中で標的物質に対して配置すること;および
標的物質を含むまたは標的物質に近接する領域に外部誘発信号を適用して、標的化部分による生体物質の被覆構造から標的物質への放出を引き起こすことを含む、請求項19に記載の方法。 - 静電的相互作用により互いに結合するポリマー材料および生体物質を含む内部材料構造であって、正味表面電荷を有する複数の領域を含む前記内部材料構造;ならびに
内部構造材料をカプセル化し、それによりカプセル化された生体物質の生物活性を保存する、生体適合性材料により形成された外部ナノ構造を含む、生物活性ペイロード送達デバイス。 - 外部ナノ構造が、生物活性ペイロード送達デバイスが配置される環境において、pH、温度、圧力、および化学物質を含む外部環境因子による分解から生体物質を保護する、請求項21に記載のデバイス。
- 外部ナノ構造の外面が、生物活性ペイロード送達デバイスが他の組織と比較して腫瘍領域に選択的に蓄積されるようにする腫瘍標的化リガンドにより官能基化されている、請求項21に記載のデバイス。
- 外部ナノ構造の外面が、望まれない体内組織、器官および系による取り込みを減少させることにより循環時間を増加させる薬剤により官能基化されており、前記薬剤がポリエチレングリコール、双性イオン化合物、または細胞膜などの患者特異的コーティングのうちの少なくとも1つを含む、請求項21に記載のデバイス。
- 生体物質が、ウイルス、細菌、タンパク質、酵素、プロドラッグ、またはDNAもしくはRNAを含む核酸ベクターを含む、請求項21に記載のデバイス。
- 生体適合性材料がシリカを含む、請求項21に記載のデバイス。
- さらに、外部ナノ構造の内側に超音波が誘発するキャビテーションの中心を作るために内部材料構造と結合した音波増感剤を含む、請求項21に記載のデバイス。
- 音波増感剤がフルオロカーボンナノエマルションを含む、請求項27に記載のデバイス。
- 生体中に配置された時に、デバイスの外部ナノ構造が適用された音波パルスに基づいて破裂して、生体内に生体物質を放出する、請求項27に記載のデバイス。
- さらに、外部ナノ構造の外面上にポリエチレングリコール(PEG)により形成された外部コーティングを含み、前記外部コーティングが、デバイスが配置された時に生体内の免疫系応答を阻止することができる、請求項21に記載のデバイス。
- さらに、外部ナノ構造の外面上に形成された標的化リガンドを含み、前記標的化リガンドが、デバイスが配置された時に生体の細胞または組織の特定の領域に選択的に結合することができる、請求項21に記載のデバイス。
- さらに、外部ナノ構造の外面上に形成された環境感知部分を含み、前記環境感知部分が、デバイスが配置された局所環境における酸化還元反応、低酸素反応、または酸性のpHのうちの少なくとも1つに基づいて化学的に形態を変化させて生体物質を放出することができる、請求項21に記載のデバイス。
- 生体物質をカプセル化する方法であって、
生物学的構造の上に生体適合性材料を形成して生物学的構造を封入する被覆構造を形成することを含み、前記被覆構造はナノメートル領域のサイズを有し、
前記生物学的構造が前記被覆構造内で生物活性を保存する、前記方法。 - 生体適合性材料がシリカを含む、請求項33に記載の方法。
- さらに、生体物質とポリカチオン性ポリマー材料とを交差反応させることにより生物学的構造の複数の領域に正に荷電した表面を形成することを含む生物学的構造の形成を含む、請求項33に記載の方法。
- 生体物質が、ウイルス、細菌、タンパク質、酵素、プロドラッグ、またはDNAもしくはRNAを含む核酸ベクターのうちの少なくとも1つを含む、請求項35に記載の方法。
- ポリカチオン性ポリマー材料がポリ-L-リシンを含む、請求項35に記載の方法。
- 被覆構造の形成が、生物学的構造の表面上への直接の電荷媒介シリカゾル-ゲル縮合反応を含み、形成された被覆構造が生物学的構造をカプセル化する外被シリカマトリックスを含む、請求項35に記載の方法。
- さらに、生物学的材料を生物学的構造の上に形成する前に生物学的構造に増感剤を結合して、被覆構造の内側に超音波が誘発するキャビテーションの中心を作ることを含む、請求項33に記載の方法。
- 増感剤がフルオロカーボンナノエマルションを含む、請求項39に記載の方法。
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