Amikacin@SiO2 core@shell nanocarriers to treat pulmonal bacterial infections.

AMC@SiO2 core@shell nanocarriers (AMC: amikacin) are realized and contain an exceptionally high drug load of 0.8 mg mg-1 (i.e. 80% AMC of total nanocarrier mass). They are prepared via a solvent-antisolvent approach with AMC nanoparticles formed in a first step, which are then covered and stabilised by a thin silica shell in a one-pot synthesis. In total, the core@shell nanocarriers exhibit a mean diameter of 240 nm with an inner AMC core of 200 nm and an outer silica shell of 20 nm. Subsequent to synthesis, the nanocarriers can be stored in frozen dimethylsulfoxide (DMSO) and applied directly after warming to room temperature with particle contents of 5 mg mL-1. Size, structure, and composition of the AMC@SiO2 core@shell nanocarriers are evidenced by electron microscopy (SEM, TEM), spectroscopic methods (EDXS, FT-IR, UV-Vis), as well as X-ray powder diffraction and elemental analysis. As proof-of-concept, the AMC release and the activity of the novel nanocarriers are tested against two relevant, difficult-to-treat and notoriously multidrug resistant, bacterial pathogens: Mycobacterium tuberculosis (M.tb.) and Mycobacterium abscessus (M.abs.). Colloidal stability, storage stability, high drug load, and activity of the AMC@SiO2 core@shell nanocarriers are promising for, e.g., aerosol-type pulmonal application.

Inverse Vulcanization of Norbornenylsilanes: Soluble Polymers with Controllable Molecular Properties via Siloxane Bonds.

The inverse vulcanization produces high sulfur content polymers from alkenes and elemental sulfur. Control over properties such as the molar mass or the solubility of polymers is not well established, and existing strategies lack predictability or require large variations of the composition. Systematic design principles are sought to allow for a targeted design of materials. Herein, we report on the inverse vulcanization of norbornenylsilanes (NBS), with a different number of hydrolysable groups at the silicon atom. Inverse vulcanization of mixtures of NBS followed by polycondensation yielded soluble high sulfur content copolymers (50 wt % S) with controllable weight average molar mass (MW ), polydispersity (D), glass transition temperature (TG ), or zero-shear viscosity (η0 ). Polycondensation was conducted in the melt with HCl as a catalyst, abolishing the need for a solvent. Purification by precipitation afforded polymers with a greatly reduced amount of low molar mass species.

Spray-dried lactose-leucine microparticles for pulmonary delivery of antimycobacterial nanopharmaceuticals.

Pulmonary delivery of nanocarriers for novel antimycobacterial compounds is challenging because the aerodynamic properties of nanomaterials are sub-optimal for such purposes. Here, we report the development of dry powder formulations for nanocarriers containing benzothiazinone 043 (BTZ) or levofloxacin (LVX), respectively. The intricacy is to generate dry powder aerosols with adequate aerodynamic properties while maintaining both nanostructural integrity and compound activity until reaching the deeper lung compartments. Microparticles (MPs) were prepared using vibrating mesh spray drying with lactose and leucine as approved excipients for oral inhalation drug products. MP morphologies and sizes were measured using various biophysical techniques including determination of geometric and aerodynamic mean sizes, X-ray diffraction, and confocal and focused ion beam scanning electron microscopy. Differences in the nanocarriers' characteristics influenced the MPs' sizes and shapes, their aerodynamic properties, and, hence, also the fraction available for lung deposition. Spay-dried powders of a BTZ nanosuspension, BTZ-loaded silica nanoparticles (NPs), and LVX-loaded liposomes showed promising respirable fractions, in contrast to zirconyl hydrogen phosphate nanocontainers. While the colloidal stability of silica NPs was improved after spray drying, MPs encapsulating either BTZ nanosuspensions or LVX-loaded liposomes showed the highest respirable fractions and active pharmaceutical ingredient loads. Importantly, for the BTZ nanosuspension, biocompatibility and in vitro uptake by a macrophage model cell line were improved even further after spray drying.