Approaching Piezoelectric Response of Pb-Piezoelectrics in Hydrothermally Synthesized Bi_0.5(Na_1–<i>x</i>K_<i>x</i>)_0.5TiO₃ Nanotubes

A large piezoelectric coefficient of 76 pm/V along the diameter direction, approaching that of lead-based piezoelectrics, is observed in hydrothermally synthesized Pb-free Bi_0.5(Na_0.8K_0.2)_0.5TiO₃ nanotubes. The 30–50 nm diameter nanotubes are formed through a scrolling and wrapping mechanism without the need of a surfactant or template. A molar ratio of KOH/NaOH = 0.5 for the mineralizers yields the Na/K ratio of ∼0.8:0.2, corresponding to an orthorhombic–tetragonal (O–T) phase boundary composition. X-ray diffraction patterns along with transmission electron microscopy analysis ascertain the coexistence of orthorhombic and tetragonal phases with (110) and (001) orientations along the nanotube length direction, respectively. ²³Na NMR spectroscopy confirms the higher degree of disorder in Bi_0.5(Na_1–<i>x</i>K_<i>x</i>)_0.5TiO₃ nanotubes with O–T phase coexistence. These findings present a significant advance toward the application of Pb-free piezoelectric materials

Superior Chemotherapeutic Benefits from the Ruthenium-Based Anti-Metastatic Drug NAMI‑A through Conjugation to Polymeric Micelles

Macromolecular ruthenium complexes are a promising avenue to better, and more selective, chemotherapeutics. NAMI-A is a ruthenium­(III) drug in Phase II clinical trials that has low cytotoxicity and is inactive against primary tumors. However, it displays both antiangiogenic and anti-invasive properties and has been shown to specifically target tumor metastases, preventing both development and growth. To increase the cytotoxicity and cell uptake of this promising drug, we designed a biocompatible amphiphilic block copolymer capable of self-assembling into polymeric micelles. An appropriate method for the synthesis of a macromolecular NAMI-A drug was identifiedthe polymerization of vinyl imidazole and subsequent addition of a ruthenium­(III) precursor complex. The cytotoxicity of these polymeric moieties was tested on ovarian cancer A2780 and Ovcar-3 and pancreatic AsPC-1 cancer cell lines. On average, across the tested cell lines, a 1.5 times increase in toxicity was found for the NAMI-A copolymer micelles when compared to the NAMI-A molecule. Furthermore, the antimetastatic potential was assessed by evaluating the inhibitory effects on the migration and invasion of cells against three cell lines characterized by differing degrees of malignancy (MDA-MB-231 > MCF-7 > CHO). The NAMI-A micelles were shown to have an improved antimetastatic potential in comparison to NAMI-A

Millisecond Self-Assembly of Stable Nanodispersed Drug Formulations

We report the development of a new spray-drying and nanoparticle assembly process (SNAP) that enables the formation of stable, yet rapidly dissolving, sub-200 nm nanocrystalline particles within a high <i>T</i>_g glassy matrix. SNAP expands the class of drugs that spray-dried dispersion (SDD) processing can address to encompass highly crystalline, but modestly hydrophobic, drugs that are difficult to process by conventional SDD. The process integrates rapid precipitation and spray-drying within a custom designed nozzle to produce high supersaturations and precipitation of the drug and high <i>T</i>_g glassy polymer. Keeping the time between precipitation and drying to tens of milliseconds allows for kinetic trapping of drug nanocrystals in the polymer matrix. Powder X-ray diffraction, solid state 2D NMR, and SEM imaging shows that adding an amphiphilic block copolymer (BCP) to the solvent gives essentially complete crystallization of the active pharmaceutical ingredient (API) with sub-200 nm domains. In contrast, the absence of the block copolymer results in the API being partially dispersed in the matrix as an amorphous phase, which can be sensitive to changes in bioavailability over time. Quantification of the API–excipient interactions by 2D ¹³C–¹H NMR correlation spectroscopy shows that the mechanism of enhanced nanocrystal formation is not due to interactions between the drug and the BCP, but rather the BCP masks interactions between the drug and hydrophobic regions of the matrix polymers. BCP-facilitated SNAP samples show improved stability during aging studies and rapid dissolution and release of API <i>in vitro</i>