公开(公告)号：US20070172520A1

公开(公告)日：2007-07-26

申请号：US11561639

申请日：2006-11-20

申请人： Michael VanAuker ,  Anna Plaas ,  Elizabeth Hood

发明人： Michael VanAuker ,  Anna Plaas ,  Elizabeth Hood

IPC分类号： A61K39/395 ,  A61K9/127

CPC分类号： A61K39/00 ,  A61K9/1272 ,  A61K39/44 ,  A61K47/6913

摘要： An immunoniosmes for targeted delivery of therapeutic agents to specific tissues in a host and methods of synthesis of those niosomes. An antibody molecule having specificity for a target antigen, such as a cell surface marker or other marker differentially expressed on a target cell, is covalently coupled to a functionalized membrane constituent. In a particular embodiment the functionalized membrane constituent is polyoxyethylene sorbitan monostearate functionalized with cyanuric chloride. The niosomes of this invention thus provide a composition that enhances internalization or retention of the bioactive agent of the niosome into the cytoplasm of the cells of the target tissue by providing a high degree of target specificity. Furthermore, the membrane vesicle enhances the life of the therapeutic agent by preventing its degradation in the extracellular environment, while exhibiting lower toxicity than can occur with some liposomes. The niosomes of the present invention are thus particularly useful as vehicles for the delivery of therapeutics to specific target cells.

摘要翻译： 将治疗剂靶向递送到宿主中的特定组织的免疫组织和合成这些niosomes的方法。 对靶抗原（例如细胞表面标志物或靶细胞上差异表达的其他标记物）具有特异性的抗体分子与官能化的膜成分共价偶联。 在一个具体实施方案中，官能化膜组分是用氰尿酰氯官能化的聚氧乙烯脱水山梨醇单硬脂酸酯。 因此，本发明的niosomes提供了一种组合物，其通过提供高度的靶特异性来增强niosome的生物活性剂的内化或保留到靶组织的细胞的细胞质中。 此外，膜囊泡通过防止其在细胞外环境中的降解来增强治疗剂的寿命，同时表现出比一些脂质体可能发生的毒性更低的毒性。 因此，本发明的niosomes特别可用作将治疗剂递送到特定靶细胞的载体。

公开(公告)号：US08435558B1

公开(公告)日：2013-05-07

申请号：US13185100

申请日：2011-07-18

申请人： Elizabeth Hood ,  Joel A. Strom ,  Michael VanAuker

发明人： Elizabeth Hood ,  Joel A. Strom ,  Michael VanAuker

IPC分类号： A61K9/127 ,  A61K9/48

CPC分类号： A61K9/1272 ,  A61K9/0009 ,  A61K41/0028 ,  A61K49/0002 ,  A61K49/22

摘要： A method of targeted drug delivery and imaging using nonionic surfactant vesicles (niosomes) in combination with ultrasound is presented. Niosomes have potential applications in targeted drug delivery and imaging because of their ability to encapsulate therapeutic agents and their enhanced uptake by physiological membranes. The niosomes may be administered to the subject via catheter. Ultrasound may be used to mediate delivery non-invasively by altering the niosome membrane structure. Niosomes composed of polyoxyethylene sorbitan monostearate (Tween 61), cholesterol, and dicetyl phosphate were synthesized via a thin film hydration technique and used for encapsulation studies. Carboxyfluorescein dye (CF) was used as a drug model to demonstrate delivery. The amount of dye in the niosomes, the concentration of the vesicles, and their mean particle size after each 5 minute incremental exposure to ultrasound was monitored. It was found that ultrasound at specific frequencies can reversibly permeabilize the lipid membrane of niosomes to allow the controlled release of a compound without destroying the niosome structure.

摘要翻译： 提出了一种使用非离子表面活性剂囊泡（niosomes）与超声结合的靶向药物递送和成像方法。 Niosomes由于其能够包封治疗剂和增强生理膜吸收的能力，在靶向药物递送和成像中具有潜在应用。 可以通过导管向受试者施用niosomes。 超声波可用于通过改变niosome膜结构非侵入性地介导递送。 通过薄膜水合技术合成由聚氧乙烯脱水山梨醇单硬脂酸酯（吐温61），胆固醇和磷酸二鲸蜡酯组成的纳米粒子，用于封装研究。 使用羧基荧光素染料（CF）作为药物模型来证明递送。 监测niosomes中的染料量，囊泡浓度及每5分钟增加暴露于超声波后的平均粒径。 发现特定频率的超声波可以可逆地渗透niosomes的脂质膜，以允许化合物的受控释放而不破坏niosome结构。

公开(公告)号：US20080050445A1

公开(公告)日：2008-02-28

申请号：US11737271

申请日：2007-04-19

申请人： Norma Alcantar ,  Kristina Dearborn ,  Michael VanAuker ,  Ryan Toomey ,  Elizabeth Hood

发明人： Norma Alcantar ,  Kristina Dearborn ,  Michael VanAuker ,  Ryan Toomey ,  Elizabeth Hood

IPC分类号： A61K9/50

CPC分类号： A61K9/0014 ,  A61K9/0085 ,  A61K47/36

摘要： Taught herein is a drug-delivery system that includes encapsulating a therapeutic drug in a nanoparticle vesicle that is then embedded into a hydrogel network. The system allows for enhanced, two-fold control over the release rate of the drug. This technology will be particularly advantageous in treating malignant cancer cells such as those found in the brain. The invention will allow for decreased side effects and increased survival time in patients. This invention opens the door to other technological applications that require controlled release of chemical substances.

摘要翻译： 本文所述是药物递送系统，其包括将治疗药物包封在纳米颗粒囊泡中，然后将其嵌入水凝胶网络中。 该系统允许对药物的释放速率进行增强的双重控制。 该技术在治疗恶性癌细胞如脑中发现的这些细胞方面特别有利。 本发明将允许患者的副作用减少和生存时间增加。 本发明为需要化学物质控制释放的其他技术应用打开了大门。

公开(公告)号：US07981442B2

公开(公告)日：2011-07-19

申请号：US11427034

申请日：2006-06-28

申请人： Elizabeth Hood ,  Joel A. Strom ,  Michael VanAuker

发明人： Elizabeth Hood ,  Joel A. Strom ,  Michael VanAuker

IPC分类号： A61K9/127 ,  A61K9/48

CPC分类号： A61K9/1272 ,  A61K9/0009 ,  A61K41/0028 ,  A61K49/0002

摘要： A method of targeted drug delivery and imaging using nonionic surfactant vesicles (niosomes) in combination with ultrasound. Niosomes have potential applications in targeted drug delivery and imaging because of their ability to encapsulate therapeutic agents and their enhanced uptake by physiological membranes. Ultrasound may be used to mediate delivery non-invasively by altering the niosome membrane structure. Niosomes composed of polyoxyethylene sorbitan monostearate (Tween 61), cholesterol, and dicetyl phosphate were synthesized via a thin film hydration technique and used for encapsulation studies. Carboxyfluorescein dye (CF) was used as a drug model to demonstrate delivery. The amount of dye in the niosomes, the concentration of the vesicles, and their mean particle size after each 5 minute incremental exposure to ultrasound was monitored. Dye concentration in niosome samples decreased while the population and size distribution of the niosome remained largely unchanged. Ultrasound is demonstrated to enhance the rate of dye diffusion across the niosome membrane non-destructively.

摘要翻译： 使用非离子表面活性剂囊泡（niosomes）与超声波组合的靶向药物递送和成像的方法。 Niosomes由于其能够包封治疗剂和增强生理膜吸收的能力，在靶向药物递送和成像中具有潜在应用。 超声波可用于通过改变niosome膜结构非侵入性地介导递送。 通过薄膜水合技术合成由聚氧乙烯脱水山梨醇单硬脂酸酯（吐温61），胆固醇和磷酸二鲸蜡酯组成的纳米粒子，用于封装研究。 使用羧基荧光素染料（CF）作为药物模型来证明递送。 监测niosomes中的染料量，囊泡浓度及每5分钟增加暴露于超声波后的平均粒径。 niosome样品中的染料浓度下降，而niosome的人口和大小分布基本保持不变。 证明超声可以非破坏性地提高染色体在染色体膜上的扩散速率。

公开(公告)号：US20060292211A1

公开(公告)日：2006-12-28

申请号：US11427034

申请日：2006-06-28

申请人： Elizabeth Hood ,  Joel Strom ,  Michael VanAuker

发明人： Elizabeth Hood ,  Joel Strom ,  Michael VanAuker

IPC分类号： A61K9/127

CPC分类号： A61K9/1272 ,  A61K9/0009 ,  A61K41/0028 ,  A61K49/0002

摘要： A method of targeted drug delivery and imaging using nonionic surfactant vesicles (niosomes) in combination with ultrasound. Niosomes have potential applications in targeted drug delivery and imaging because of their ability to encapsulate therapeutic agents and their enhanced uptake by physiological membranes. Ultrasound may be used to mediate delivery non-invasively by altering the niosome membrane structure. Niosomes composed of polyoxyethylene sorbitan monostearate (Tween 61), cholesterol, and dicetyl phosphate were synthesized via a thin film hydration technique and used for encapsulation studies. Carboxyfluorescein dye (CF) was used as a drug model to demonstrate delivery. The amount of dye in the niosomes, the concentration of the vesicles, and their mean particle size after each 5 minute incremental exposure to ultrasound was monitored. Dye concentration in niosome samples decreased while the population and size distribution of the niosome remained largely unchanged. Ultrasound is demonstrated to enhance the rate of dye diffusion across the niosome membrane non-destructively.

摘要翻译： 使用非离子表面活性剂囊泡（niosomes）与超声波组合的靶向药物递送和成像的方法。 Niosomes由于其能够包封治疗剂和增强生理膜吸收的能力，在靶向药物递送和成像中具有潜在应用。 超声波可用于通过改变niosome膜结构非侵入性地介导递送。 通过薄膜水合技术合成由聚氧乙烯脱水山梨醇单硬脂酸酯（吐温61），胆固醇和磷酸二鲸蜡酯组成的纳米粒子，用于封装研究。 使用羧基荧光素染料（CF）作为药物模型来证明递送。 监测niosomes中的染料量，囊泡浓度及每5分钟增加暴露于超声波后的平均粒径。 niosome样品中的染料浓度下降，而niosome的人口和大小分布基本保持不变。 证明超声可以非破坏性地提高染色体在染色体膜上的扩散速率。