Preparation, Characterization, and Formulation Optimization of Ionic-Liquid-in-Water Nanoemulsions toward Systemic Delivery of Amphotericin B.

Amphotericin B (AmB) is an antifungal agent that poses a challenge for intravenous drug delivery due to its hydrophobicity and severe side effects that are attributed to the self-aggregation of AmB in aqueous solution. To overcome this problem, we have rationally designed an ionic-liquid-in-water nanoemulsion drug delivery system that harnesses the unique properties of ionic liquids. The complex drug AmB serves as a model pharmaceutical agent to demonstrate the robustness of ionic-liquid-in-water nanoemulsions. High concentrations of AmB were solubilized in a new hydrophobic dicholinium-based ionic liquid. The absorption spectrum of AmB in an ionic liquid mixture and prepared nanoemulsion indicates AmB solubilization in the monomeric form. The hydrophobic ionic liquid exhibits high in vivo biocompatibility with zebrafish. The hemolytic activity of the AmB nanoemulsion was negligible, yet it maintained antifungal activity against Candida albicans. The preliminary results presented in this Communication indicate that ionic-liquid-in-water nanoemulsions may allow for the delivery of a variety of pharmaceuticals intravenously, broadening the scope of ionic liquids in the pharmaceutical sciences.

Protein-templated gold nanoparticle synthesis: protein organization, controlled gold sequestration, and unexpected reaction products.

Emerging applications that exploit the properties of nanoparticles for biotechnology require that the nanoparticles be biocompatible or support biological recognition. These types of particles can be produced through syntheses that involve biologically relevant molecules (proteins or natural extracts, for example). Many of the protocols that rely on these molecules are performed without a clear understanding of the mechanism by which the materials are produced. We have investigated a previously described reaction in which gold nanoparticles are produced from the reaction of chloroauric acid and proteins in solution. We find that modifications to the starting conditions can alter the product from the expected solution-suspended colloids to a product where colloids are formed within a solid, fibrous protein structure. We have interrogated this synthesis, exploiting the change in products to better understand this reaction. We have evaluated the kinetics and products for 7 different proteins over a range of concentrations and temperatures. The key factor that controls the synthetic outcome (colloid or fiber) is the concentration of the protein relative to the gold concentration. We find that the observed fibrous structures are more likely to form at low protein concentrations and when hydrophilic proteins are used. An analysis of the reaction kinetics shows that AuNP formation occurs faster at lower protein (fiber-forming) concentrations than at higher protein (colloid-forming) concentrations. These results contradict traditional expectations for reaction kinetics and protein-fiber formation and are instructive of the manner in which proteins template gold nanoparticle production.

Protein-based ferrogels.

We present a novel synthesis in which hemoglobin and Fe(2+) react, in the presence of KNO3 and KOH, to produce protein microgels that contain magnetic iron oxide nanoparticles. The synthesis results in microgels with polymer properties (denaturing and glass transition temperatures) that are consistent with the dried protein. The iron oxide nanoparticles that exhibit an average diameter of 22nm, are ferrimagnetic, and display properties consistent with Fe3O4. The multiple functional capabilities displayed by these materials: biocompatibility, magnetism, dye uptake and controlled release, and other properties archetypal of hydrogels, will make the magnetic hydrogels attractive for a number of biomedical applications.