Summary: Polypyrrole nanotubes with high electric conductivity and azo function have been fabricated in high yield via an in‐situ polymerization. During the process fibrillar complex of FeCl3 and methyl orange (MO), acting as a reactive self‐degraded template, directed the growth of polypyrrole on its surface and promoted the assembly into hollow nanotubular structures.TEM image of uncompleted PPy nanotubes synthesized in MO solutions after reaction for 40 min.magnified imageTEM image of uncompleted PPy nanotubes synthesized in MO solutions after reaction for 40 min.

Johnson and Prud'homme (2003. AICHE J 49:2264-2282) introduced the confined impingement jets (CIJ) mixer to prepare nanoparticles loaded with hydrophobic compounds (e.g., drugs, inks, fragrances, or pheromones) via flash nanoprecipitation (FNP). We have modified the original CIJ design to allow hand operation, eliminating the need for a syringe pump, and we added a second antisolvent dilution stage. Impingement mixing requires equal flow momentum from two opposing jets, one containing the drug in organic solvent and the other containing an antisolvent, typically water. The subsequent dilution step in the new design allows rapid quenching with high antisolvent concentration that enhances nanoparticle stability. This new CIJ with dilution (CIJ-D) mixer is a simple, cheap, and efficient device to produce nanoparticles. We have made 55 nm diameter β-carotene nanoparticles using the CIJ-D mixer. They are stable and reproducible in terms of particle size and distribution. We have also compared the performance of our CIJ-D mixer with the vortex mixer, which can operate at unequal flow rates (Liu et al., 2008. Chem Eng Sci 63:2829-2842), to make β-carotene-containing particles over a series of turbulent conditions. On the basis of dynamic light scattering measurements, the new CIJ-D mixer produces stable particles of a size similar to the vortex mixer. Our CIJ-D design requires less volume and provides an easily operated and inexpensive tool to produce nanoparticles via FNP and to evaluate new nanoparticle formulation.

This study systematically compares the effects of amphiphilic diblock copolymer (di-BCP) on stabilizing hydrophobic drug nanoparticles formed by flash nanoprecipitation (FNP), and provides a guideline on choosing suitable di-BCPs. Four widely used di-BCPs, i.e., polystyrene-block-poly(ethylene glycol) (PS-b-PEG), polycaprolactone-block-poly(ethylene glycol) (PCL-b-PEG), polylactide-block-poly(ethylene glycol) (PLA-b-PEG), and poly(lactic-co-glycolic acid) (PLGA-b-PEG), and β-carotene as a model drug were used. The study showed that PLGA-b-PEG was the most suitable one, whose hydrophobic block was biodegradable and noncrystallizable as well as had relatively high glass transition temperature (Tg) and a right solubility parameter (δ). The molecular weight of PLGA block over the range from 5k to 15k showed an insignificant effect on controlling the particle size. Amorphous drug particles with a high drug loading of over 83 wt% can be achieved. Much remarkable evidence supported the nanoparticles with kinetically frozen and nonequilibrium packing structures of polymer chains rather than either the micelles or micellar nanoparticles with two well segregated polymer blocks. The thermodynamic effects of the drug and BCP on the particle stability, size and structures were discussed by using solubility parameters.

Flash nanoprecipitation (FNP) can generate hydrophobic drug nanoparticles in ~100 nm with a much higher drug loading (e.g., > 40 wt%) than traditional nanocarriers (e.g., < 20 wt%). This paper studies effects of drug molecules on nanoparticle stability made via FNP, and demonstrates that chemically bonding a drug compound (e.g., paclitaxel) with a cleavable hydrophobic moiety of organosilicate (e.g., triethoxysilicate) is able to enhance the particle size stability. Poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) (PLGA-b-PEG) is used as a model surfactant to provide steric stabilization. The experiments showed that the lower the drug solubility in the aqueous medium, the more stable the particles in terms of Ostwald ripening, which are consistent with the prediction by the LSW theory. To correlate the particle stability with hydrophobicity, this study introduces the n-octanol/water partition coefficient (LogP), a hydrophobicity indication, into the FNP technique. A comparison of various drugs and their analogs shows that LogP of a drug is a better hydrophobicity indication than solubility parameter (δ) and well correlates with the particle stability. Empirically, with ACDLogP > ~12, nanoparticles have good stability; with ~2 < ACDLogP < ~9, nanoparticles show fast Ostwald ripening and inter-particle recrystallization; with ACDLogP < ~2, the drug is very likely difficult to form nanoparticles. This rule creates a quick way to predict particle stability for a randomly selected drug structure, and helps a fast preclinical screen for FNP.

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