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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.

An electrospray method is developed for preparation of beclomethasone-dipropionate- and salbutamol-sulfate-loaded biodegradable poly(L-lactic acid) nanoparticles. Different set-up parameters for electrospraying are examined on particle size, and preparation conditions are optimized for producing spherical-drug-loaded nanoscale particles by controllable processing parameters. Polylactide (PLA)-drug nanoparticles with average diameters of around 200 nm are achieved in a stable cone-jet mode with a flow rate of 4 microL min(-1), polymer concentration of 1%, and ammonium hydroxide content of 0.05%. Morphology and size of the drug-polymer nanoparticles are analyzed by scanning electron microscopy and transmission electron microscopy. Changes in the crystallinity of the PLA polymer and the model drugs are detected by X-ray powder diffraction, and the absence of molecular interactions are confirmed by thermal analyses. The results indicate clearly that electrospraying is a potential method for producing polymeric nanoparticles and for encapsulating both hydrophilic and hydrophobic drugs efficiently into the nanoparticles.

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The most important advantage of these techniques as compared with many other particle formation techniques is that the production of dried powders is possible without any extra drying step.

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