When a solute is present in an aqueous droplet, the water activity in the droplet and the rate of droplet dissolution are both decreased (as compared to a pure water droplet). One of the main parameters that controls this effect is the dynamically changing solute concentration, and therefore water activity and chemical potential, at the droplet interface. This work addresses the importance of understanding how water activity changes during solution droplet dissolution. A model for dissolution rate is presented that accounts for the kinetic effects of changing water activity at the droplet interface during the dissolution of an aqueous salt solution microdroplet into a second immiscible liquid phase. The important underlying question in this model is whether the dissolving component can be considered in local equilibrium on both sides of the droplet interface and whether this assumption is sufficient to account for the kinetics of dissolution. The dissolution model is based on the Epstein-Plesset equation, which has previously been applied to pure gas (bubble) and liquid (droplet) dissolution into liquid phases, but not to salt solutions. The model is tested by using the micropipet technique to form and observe the dehydration of single NaCl solution microdroplets in octanol or butyl acetate. The model successfully predicts the droplet diameter as a function of time in both organic solvents. The NaCl concentration in water is measured well into the supersaturated area >5.4 M, and the supersaturation limit at which NaCl nucleation happens is reported to be 10.24 ± 0.31 M.

The story starts in Basel at CLINAM in 2013, when I asked Pieter about making nanoparticles and he advised me to "try this solvent-exchange method we have developed for making limit sized particles". We are particularly interested in what are "limit size materials" because we want to test the feasibility of an idea: could we design, make, develop, and test the concept for treating metastatic cancer by, "Putting the Drug in the Cancer's Food? "Limit size" is the size of the cancer's food, ? the common Low Density Lipoprotein, (LDL) ~20 nm diameter. In this contribution to Pieter's LTAA we focus on the "bottom" (nucleation) and the "up" (growth) of "bottom-up design" as it applies to homogeneous nucleation of especially, hydrophobic drugs and the 8 physico-chemical stages and associated parameters that determine the initial size, and any subsequent coarsening, of a nanoparticle suspension. We show that, when made by the rapid solvent-exchange method, the same sized particles can be obtained without phospholipid. Furthermore, the obtained size follows the predictions of classic nucleation theory when the appropriate values for the parameters (surface tension and supersaturation) at nucleation are included. Calculations on dissolution time for nanoparticles reveal that a typical fewmicromolar-solubility, hydrophobic, anti-cancer drug (like Lapatinib, Niclosamide, Abiraterone, and Fulvestrant) of 500 nm diameter would take between 3?7 s to dissolve in an infinite sink like the blood stream; and a 50 nm particle would dissolve in less than a second! And so the nanoparticle design requires a highly water-insoluble drug, and a tight, encapsulating, impermeable lipid:cholesterol monolayer. While the "Y" junction can be used to mix an ethanolic solution with anti-solvent, we find that a "no-junction" can give equally good results. A series of nanoparticles (DiI-fluorescently labeled Triolein-cored and drug-cored nanoparticles of Orlistat) were then tested in well-characterized cell lines for uptake and efficacy as well as a PET-imageable nanoparticle in initial PET-imaging studies in animals for EPR uptake and tumor detection. We show that, while free-drug cannot be optimally administered in vivo, a nanoparticle formulation of orlistat could in principle represent a stable parenteral delivery system. The article ends with a brief discussion of what we see as the way forward in Individualized Medicine from the Diagnostic-Therapeutic ("Diapeutic") side, requiring FDG detection of metastatic lesions, functional imaging of a protein target (e.g. Fatty Acid Synthase) usingC acetate, then a PET (or other)-imageable nanoparticle to demonstrate EPR accumulation, and then the administration of the pure-drug nanoparticle taken in by the most aggressive cancer cells in the perivascular space, as they would their "food".

This review presents a series of measurements of the surface and interfacial tensions we have been able to make using the micropipette technique. These include: equilibrium tensions at the air-water surface and oil-water interface, as well as equilibrium and dynamic adsorption of water-soluble surfactants and water-insoluble and lipids. At its essence, the micropipette technique is one of capillary-action, glass-wetting, and applied pressure. A micropipette, as a parallel or tapered shaft, is mounted horizontally in a microchamber and viewed in an inverted microscope. When filled with air or oil, and inserted into an aqueous-filled chamber, the position of the surface or interface meniscus is controlled by applied micropipette pressure. The position and hence radius of curvature of the meniscus can be moved in a controlled fashion from dimensions associated with the capillary tip (~5–10 μm), to back down the micropipette that can taper out to 450 μm. All measurements are therefore actually made at the microscale. Following the Young–Laplace equation and geometry of the capillary, the surface or interfacial tension value is simply obtained from the radius of the meniscus in the tapered pipette and the applied pressure to keep it there. Motivated by Franklin’s early experiments that demonstrated molecularity and monolayer formation, we also give a brief potted-historical perspective that includes fundamental surfactancy driven by margarine, the first use of a micropipette to circuitously measure bilayer membrane tensions and free energies of formation, and its basis for revolutionising the study and applications of membrane ion-channels in Droplet Interface Bilayers. Finally, we give five examples of where our measurements have had an impact on applications in micro-surfaces and microfluidics, including gas microbubbles for ultrasound contrast; interfacial tensions for micro-oil droplets in oil recovery; surface tensions and tensions-in-the surface for natural and synthetic lung surfactants; interfacial tension in nanoprecipitation; and micro-surface tensions in microfluidics.