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COMPOSITIONS AND METHODS FOR OPTIMIZING DRUG HYDROPHOBICITY AND DRUG DELIVERY TO CELLS
COMPOSITIONS AND METHODS FOR OPTIMIZING DRUG HYDROPHOBICITY AND DRUG DELIVERY TO CELLS
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机译:用于优化药物疏水性和药物向细胞递送的组合物和方法
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摘要
Methods to determine drug hydrophobicity and to quantify changes in drug hydrophobicity that optimize drug function by means of differential scanning calorimetry of an endothermic phase transition of a base protein-based polymer, specifically of an elastic-contractile model protein, to which is attached the drug to be evaluated for its hydrophobicity in terms of the change in Gibbs free energy for hydrophobic association, ΔGHA have been developed. Also described herein is the preparation of nanoparticles comprised of protein-based polymers, specifically of elastic-contractile model proteins, designed for the binding and desired release rate of a specific drug or class of drugs. Further described herein is a means of targeting the drug-laden nanoparticle to a cell by means of decorating the nanoparticle surface with a molecular entity that selectively binds to the diseased cell or disease causing organism, e.g., by decorating the drug-laden nanoparticle surface with synthetic antigen-binding fragment to an up-regulated receptor characteristic of the diseased cell.
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机译:确定药物疏水性并量化药物疏水性变化的方法,该方法可通过差示扫描量热法对附着有该药物的基础蛋白基聚合物(尤其是弹性收缩模型蛋白)的吸热相变进行优化,从而优化药物功能为了根据疏水缔合的吉布斯自由能的变化来评价其疏水性,已经开发了ΔG HA Sub>。本文还描述了纳米颗粒的制备,该纳米颗粒包含基于蛋白质的聚合物,特别是弹性收缩模型蛋白,其设计用于特定药物或一类药物的结合和所需的释放速率。本文进一步描述了通过用选择性结合患病细胞或致病生物的分子实体修饰纳米颗粒表面,例如通过用以下修饰修饰药物负载纳米颗粒表面,将载药纳米颗粒靶向细胞的方法:合成抗原结合片段至患病细胞特征的上调受体。
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