Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties.

Sorafenib, marketed under the brand name Nexavar®, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil® 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. In vivo study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib's bioavailability and outlines potential translational directions for oral drug development.

Ovonic threshold switching in polycrystalline zinc telluride thin films deposited by RF sputtering.

Chalcogenide materials of the amorphous phase with low band gaps were reported to show Ovonic threshold switching (OTS), making them suitable for selection devices in cross-point memory arrays. Herein, we report that ZnTe films with polycrystalline structures show OTS behavior. Nearly stoichiometric ZnTe thin films were deposited by an RF sputtering method. X-ray diffraction analysis indicated that the films were polycrystalline. The optical band gaps of the ZnTe films were estimated as 2.2 eV from UV-visible spectroscopy transmittance measurements. Photoluminescence measurements indicated the existence of deep-level defects in the ZnTe thin films. Although these ZnTe films have a polycrystalline structure with a relatively high band gap, I-V profiles show OTS characteristics, with a selectivity of over 104, fast threshold switching time in the sub-10 ns scale, and thermal stability up to 400 °C. ZnTe also shows switching endurance for more than 109 cycles without Vth drift, maintaining its selectivity of 104. Thus, we improved the threshold switching characteristics by using a wide band-gap and polycrystalline-structured ZnTe-based chalcogenide material. Post-annealing experiments indicated that the thermal budget of the ZnTe thin film was sufficient for stacked cross-point array structures, thereby overcoming a previous limitation of chalcogenide switching materials. This material is promising for application in high-density cross-point memory arrays as the selection device.

Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug.

Introduction: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. Methods: Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. Results: When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. Discussion: Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug.

Recent Advances in pH- or/and Photo-Responsive Nanovehicles.

The combination of nanotechnology and chemotherapy has resulted in more effective drug design via the development of nanomaterial-based drug delivery systems (DDSs) for tumor targeting. Stimulus-responsive DDSs in response to internal or external signals can offer precisely controlled delivery of preloaded therapeutics. Among the various DDSs, the photo-triggered system improves the efficacy and safety of treatment through spatiotemporal manipulation of light. Additionally, pH-induced delivery is one of the most widely studied strategies for targeting the acidic micro-environment of solid tumors. Accordingly, in this review, we discuss representative strategies for designing DDSs using light as an exogenous signal or pH as an endogenous trigger.

Deformable Ionic Polymer Artificial Mechanotransducer with an Interpenetrating Nanofibrillar Network.

We demonstrate an ionic polymer artificial mechanotransducer (i-PAM) capable of simultaneously yielding an efficient wide bandwidth and a blocking force to maximize human tactile recognition in soft tactile feedback. The unique methodology in the i-PAM relies on an ionic interpenetrating nanofibrillar network that is formed at the interface of (i) an ionic thermoplastic polyurethane nanofibrillar matrix with an ionic liquid of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([EMIM]+[TFSI]-) and (ii) ionic poly(3,4-ethylenedioxythiophene):poly(styrenesulfonic acid) (PEDOT:PSS) conducting polymer electrodes with dimethyl sulfoxide and [EMIM]+[TFSI]- as additives. The i-PAM-based actuator with the ionic PEDOT:PSS exhibits a stable operation up to 200 Hz at low voltage as well as a blocking force of 0.4 mN, which can be potentially adapted to soft tactile feedback. Furthermore, on the basis of this fast i-PAM, we realized alphabet tactile rendering by using a 3 × 3 i-PAM array stimulated by a dc input of 2 V. We believe that our proposed approach can provide a rational guide to the human-machine soft haptic interface.

Intra-hospital transport of critically ill patients with rapid response team and risk factors for cardiopulmonary arrest: A retrospective cohort study.

INTRODUCTION: This study aimed to determine the occurrence rate and risk factors of cardiopulmonary arrest (CPA) during intra-hospital transport (IHT) among critically ill patients, accompanied by a rapid response team (RRT). METHODS: We performed a retrospective cohort study in a 1300-bed tertiary-care teaching hospital. Data of all admitted patients transported within the hospital and accompanied by the RRT from October 2012 to May 2016 were included. We compared patients with CPA (+) and patients without CPA (-) to identify risk factors for CPA during transport. RESULTS: Among 535 patients, CPA occurred in eight (1.5%) patients during IHT. There were no significant differences in age, sex, and comorbidities between groups. More patients in the CPA (+) group than in the CPA (-) group received manual ventilation during IHT (75% vs. 23.0%, p = 0.001). An increased risk of CPA (p<0.001) corresponded with a higher number of vasopressors used during IHT. In univariate logistic regression analysis, history of myocardial infarction (OR 10.7, 95% CI 2.4-50.5, p = 0.005), manual ventilation (OR 10.1, 95% CI 2.0-50.5, p = 0.005), and use of three or more vasopressors (OR 11.1, 95% CI 2.5-48.9, p = 0.001) were significantly associated with risk of CPA during RRT-led IHT. CONCLUSIONS: Despite accompaniment by a specialized team such as the RRT, CPA can occur during IHT. History of myocardial infarction, manual ventilation with bag-valve mask, and the use of three or more vasopressors were independent risk factors of CPA during IHT of critically ill patients accompanied by the RRT.