Amorphization and modified release of ibuprofen by post-synthetic and solvent-free loading into tailored silica aerogels

Promising active pharmaceutical ingredients (APIs) often exhibit poor aqueous solubility and thus a low bioavailability that substantially limits their pharmaceutical application. Hence, efficient formulations are required for an effective translation into highly efficient drug products. One strategy is the preservation of an amorphous state of the API within a carrier matrix, which leads to enhanced dissolution. In this work, mesoporous silica aerogels (SA) were utilized as a carrier matrix for the amorphization of the poorly water-soluble model drug ibuprofen. Loading of tailored SA was performed post-synthetically and solvent-free, either by co-milling or via the melting method. Thorough analyses of these processes demonstrated the influence of macrostructural changes during the drying and grinding process on the microstructural properties of the SA. Furthermore, interfacial SA-drug interaction properties were selectively tuned by attaching terminal hydrophilic amino- or hydrophobic methyl groups to the surface of the gel. We demonstrate that not only the chemical surface properties of the SA, but also formulation-related parameters, such as the carrier-to-drug ratio, as well as process-related parameters, such as the drug loading method, decisively influence the ibuprofen adsorption efficiency. In addition, the drug-loaded SA formulations exhibited a remarkable physical stability over a period of 6 months. Furthermore, the release behavior is shown to change considerably with different surface properties of the SA matrix. Hence, the reported results demonstrate that utilizing specifically processed and modified SA offers a compelling technique for enhancement of the bioavailability of poorly-water soluble APIs and a versatile adjustment of their release profile.     

Evolution of thrombolytic therapy in patients with HeartWare ventricular assist device thrombosis: a single-institutional experience

Open in a separate window OBJECTIVESPump thrombosis remains a major challenge in heart failure patients with left ventricular HeartWare assist device. Current International Society for Heart and Lung Transplantation recommendations favour surgical pump exchange over lysis because safety and efficacy of lysis has been controversially reported. This study summarizes our experience on our HeartWare thrombosis prevention strategy as well as thrombolysis through implementation of our institutional standardized HeartWare assist device protocol.METHODSOutcomes of all HeartWare thrombosis patients admitted between 2010 and 2020 were analysed. Thrombolysis therapy using tissue plasminogen activator was used as the first-line therapy in this study and thrombolysis therapy efficacy was defined as freedom from stroke, bleeding, recurrent HeartWare assist device thrombosis or surgical device exchange within 30 days after lysis application.RESULTSA total of 507 patients have been included in this study and 66 patients (13%) collectively developed a first HeartWare-thrombosis after a median of 12 months (8–22 months) after HeartWare implantation. Forty patients were treated with unstandardized lysis, of whom 7 patients had thrombolysis associated complications, such as incomplete thrombus resolution requiring surgical pump exchange in 4 patients, but also intracranial haemorrhage occurring in 3 patients. Three patients died in the non-protocol group. Eight device thrombosis patients were treated according to our protocol, showing no lysis-associated complication.CONCLUSIONSDespite current recommendations, preferring surgical HeartWare pump exchange in thrombosis, thrombolysis therapy for first HeartWare thrombosis can be safe and effective in a standardized protocol setting, including anticoagulation adjustment and intensified blood pressure control management.     

Automated multicolor mesoscopic imaging for the 3-dimensional reconstruction of fluorescent biomarker distribution in large tissue specimens

Research in translational medicine often requires high-resolution characterization techniques to visualize or quantify the fluorescent probes. For example, drug delivery systems contain fluorescent molecules enabling in vitro and in vivo tracing to determine biodistribution or plasma disappearance. Albeit fluorescence imaging systems with sufficient resolution exist, the sample preparation is typically too complex to image a whole organism of the size of a mouse. This article established a mesoscopic imaging technique utilizing a commercially available cryo-microtome and an in-house built episcopic imaging add-on to perform imaging during serial sectioning. Here we demonstrate that our automated red, green, blue (RGB) and fluorescence mesoscope can generate sequential block-face and 3-dimensional anatomical images at variable thickness with high quality of 6 µm × 6 µm pixel size. In addition, this mesoscope features a numerical aperture of 0.10 and a field-of-view of up to 21.6 mm × 27 mm × 25 mm (width, height, depth).     

Revision Hip Arthroplasty with A Modular Cementless Stem: Mid-Term Follow Up

Despite the increasing volume of revision total hip arthroplasty (THA) being performed in the United States, there are few studies reporting mid-term clinical and radiographic outcomes of modular fully porous-coated femoral stems. We retrospectively studied a consecutive series of patients who underwent revision THA with a modular extensively porous-coated femoral component at a single institution and by a single surgeon. The final study group included 54 hips (52 patients) followed for an average of 84 months. Ten-year survival rates with revision for any reason and revision for femoral loosening as endpoints were 94% and 100%, respectively. No complications regarding the modular junction were encountered. Of the 50 hips with adequate radiographs, all showed proximal ingrowth and 42 (84%) had both proximal and distal ingrowth. The modular, fully porous-coated femoral stem studied demonstrated excellent survivorship and bone ingrowth at mid-term follow up.     

Being in transit and in transition The experience of time at the place,when living with severe incurable disease ‐ a phenomenological study

The aim of this study is to describe the experience of time as it presents itself at the place being situated when living with severe incurable disease and receiving palliative care. The empirical data consist of 26 open‐ended interviews with 23 patients receiving palliative care at home, at a palliative day care, in a palliative bed unit in hospital or in a nursing home in Norway. A common meaning of a shifting space for living emerged from the analysis and was revealed through three different aspects: (i) Transition from a predictable to an unpredictable time: To live with severe incurable disease marks a transition to a changed life involving an ongoing weakened and altered body with bothersome symptoms making experience of time different and unpredictable. (ii) Transition between a safe and unsafe time: When time is unpredictable, feeling safe is revealed as essential to how time is experienced at the place being situated. (iii) To be in transition from a homely to a homeless existence: In a time of increased bodily weakness, unpredictable ailments and displacements, the sense of belonging to the place is revealed as significant to the experience of time. Not knowing where to be in a time of change is like an existential cry of distress where the foothold in existence is lost. The findings are discussed and interpreted as an embodied experience originating from the passage of time continually affecting life sometimes so fundamentally that it marks a transition to a changed space of life that is reflected in the experience of time.