Multifunctional Hydrophobin: Toward Functional Coatings for Drug Nanoparticles

Abstract

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.

Applications of hydrophobins: current state and perspectives

“…However, their aggregation is a major drawback to their use in electrochemical sensors and biosensors. Two-dimensional crystalline graphene sheets and multiwalled carbon nanotubes (MWCNT) were stabilized in aqueous solution by coating with the class II hydrophobin HFBI (Laaksonen et al 2010;Wang et al 2010c), while multi-and single-walled CNT, graphene sheets, and HOPG were dispersed using the class I hydrophobins HFGI (Grifola frondosa), EAS and HYD3 (Fusarium verticillioides) (Wang et al 2010d;Yang et al 2013). The hydrophobin modification is a simple, one-step process.…”

“…Hydrophobins offer a simple and generic alternative to create and stabilize nanoparticles. For instance, hydrophobins can be used in formulations of water-insoluble drugs for oral (Haas Jimoh Akanbi et al 2010;Valo et al 2010), topical (Vejnovic et al 2010a, b), and intravenous (Fang et al 2014) drug delivery. The oral bioavailability of the hydrophobic drugs cyclosporine A and nifedipine was increased 2-and 6-fold, respectively, when SC3 was added to the drug suspension (Haas Jimoh Akanbi et al 2010).…”

“…Similarly, fullerene molecules were immobilized on SC3-coated electrodes (Corvis et al 2007). Silicon surfaces and graphene sheets were functionalized with gold nanoparticles coated with mercaptosuccinic acid (MSA) via disulfide formation to cysteines of HFBI derivatives (Laaksonen et al 2009(Laaksonen et al , 2010. Interest in the fabrication of titanium thin films is increasing because of several attractive applications including microelectronic devices and photonic materials (Santhiya et al 2010).…”

Binding of Protein-Functionalized Entities onto Synthetic Vesicles

“…Data were analyzed accounting for the diffusive contributions pertinent to nano-particles and for the respective reactive terms, respectively. The results are expressed in terms of the relation (2) where I 2 (t), I 1 (0) and I 1 (t) are the scattering intensity at time t, the original value at time zero and the reactive part, respectively. DLS data were interpreted according to Berne and Pecora (24) .…”

“…Properly functionalized particles, such as quantum dots, spheres, disks, filaments, tubes and composite objects (all in the nano-meter size range) find substantial application in the aforementioned fields. In this contribution, we report on silica nano-particles, onto which a protein, lysozyme, was covalently bound (2,3) . The synthetic part of the work is reported below.…”