Suchergebnisse

The design of new multicomponent pharmaceutical materials that involve different active pharmaceutical ingredients (APIs), e.g., drug-drug cocrystals, is a novel and interesting approach to address new therapeutic challenges. In this work, the hydrochlorothiazide-caffeine (HCT–CAF) codrug and its methanol solvate have been synthesized by mechanochemical methods and thoroughly characterized in the solid state by powder and single crystal X-ray diffraction, respectively, as well as differential scanning calorimetry, thermogravimetric analyses and infrared spectroscopy. In addition, solubility and stability studies have also been performed looking for improved physicochemical properties of the codrug. Interestingly, the two reported structures show great similarity, which allows conversion between them. The desolvated HCT–CAF cocrystal shows great stability at 24 h and an enhancement of solubility with respect to the reference HCT API. Furthermore, the contribution of intermolecular forces on the improved physicochemical properties was evaluated by computational methods showing strong and diverse H-bond and π–π stacking interactions. ; Spanish Agencia Estatal de Investigacion of the Ministerio de Ciencia, Innovacion y Universidades (MICIU) ; European Union (EU) PGC2018-102047-B-I00 ; MICIU/AEI from SPAIN CTQ2017-85821-R

The search for efficient plasmonic photothermal therapies using nonharmful pulse laser irradiation at the near-infrared (NIR) is fundamental for biomedical cancer research. Therefore, the development of novel assembled plasmonic gold nanostructures with the aim of reducing the applied laser power density to a minimum through hot-spot-mediated cell photothermolysis is an ongoing challenge. We demonstrate that gold nanorods (Au NRs) functionalized at their tips with a pH-sensitive ligand assemble into oligomers within cell lysosomes through hydrogen-bonding attractive interactions. The unique intracellular features of the plasmonic oligomers allow us to significantly reduce the femtosecond laser power density and Au NR dose while still achieving excellent cell killing rates. The formation of gold tip-to-tip oligomers with longitudinal localized surface plasmon resonance bands at the NIR, obtained from low-aspect-ratio Au NRs close in resonance with 800 nm Ti:sapphire 90 fs laser pulses, was found to be the key parameter for realizing the enhanced plasmonic photothermal therapy. ; This work has been funded by the Spanish MINECO (MAT2014-59678-R and CTQ2012-37404-C02-01) and the Madrid Regional Government (S2013/MIT-2807). A.C.-M. and M.C. and I.L.-M. acknowledge the financial support of the ERC Starting Grants "NANOFORCELLS" (ERC-StG-2011-278860) and "MITOCHON" (ERC-StG-2013-338133). A.G.-M. and I.L.-M. acknowledge receipt of Ramón y Cajal Fellowships from the Spanish MINECO. G.G.-R. acknowledges receipt of the FPI Fellowship from the Spanish MINECO. ; Peer reviewed