Multifunctional Hydrophobin: Toward Functional Coatings for Drug Nartoplarticles
Multifunctional Hydrophobin: Toward Functional Coatings for Drug Nartoplarticles
复制标题
DOI：
10.1021/nn9017558
复制
发表时间：
2010-03-01
期刊：
影响因子：
17.1
通讯作者：
Laaksonen, Timo J.
中科院分区：
文献类型：
--
作者：
Valo, Hanna K.;Laaksonen, Paivi H.;Laaksonen, Timo J.
尽管药物纳米技术发展迅速，但纳米药物制剂并不总是能够有效地输送到所需的身体部位。尽管尺寸对于增加生物利用度和控制药物递送具有显著效果，但亚微米制剂还需要更深层次的设计。颗粒的表面性质决定了颗粒的稳定性、与身体的相互作用以及药物的靶向潜力。因此，可以利用纳米颗粒的表面层来增加药物的功效。影响药物的表面性质是目前工作的主要焦点，介绍了一种利用疏水蛋白（HFB）蛋白质从低溶解度药物制备具有功能位点的纳米颗粒的方法。通过在HFB蛋白存在下在水中沉淀亲脂性药物（丙酸倍氯米松）来制备颗粒。随着HFB浓度的增加，可以容易地达到低于200 nm的粒度。该颗粒在悬浮液中至少稳定5 h，冷冻干燥后可储存更长时间。使用与HFB基因融合的绿色荧光蛋白（GFP）的标记研究清楚地表明，纳米颗粒的表面覆盖有疏水蛋白，并且该表面可以通过利用融合蛋白进一步修饰。这为各种不同的功能性表面结合基团提供了模板，这些基团可以通过蛋白质生物工程修饰HFB的亲水侧来定制。本研究将蛋白质与传统制药技术相结合，合成功能化的蛋白质包覆纳米粒，用于药物释放。
Efficient delivery of nanosized drug formulations to the desired body sites is not always reached despite the rapid development of pharmaceutical nanotechnologies. In spite of the undoubted effect of the size for increased bioavailability and controlled drug delivery, submicrometer formulations also require a deeper level of design. The surface properties of the particles determine the stability of the particles, interactions with the body, and targeting potentials of drugs. Thus, the efficacy of the drug can be increased utilizing the surface layer of the nanoparticles. Influencing the surface characters of the drug is the main focus of the present work, which introduces a method for preparing nanoparticles with functional sites from low-solubility drugs using hydrophobin (HFB) proteins. Particles were prepared by precipitating a lipophilic drug (beclomethasone dipropionate) in water in the presence of the HFB proteins. Particle size below 200 nm could easily be reached with increasing HFB concentration. The particles were shown to be stable for at least 5 h in suspension, and they could be stored for longer periods of time after freeze-drying. Labeling studies using green fluorescent protein (GFP) genetically fused to a HFB clearly demonstrated that the surface of the nanoparticles was covered with the hydrophobins and that the surface could be further modified by utilizing fusion proteins. This provides a template for a variety of different functional surface-bound groups that could be tailored by modifying the hydrophilic side of the HFB via protein bioengineering. In this study, the combination of proteins and traditional pharmaceutical technology was used to synthesize functionalized protein-coated nanoparticles for drug delivery purposes.