Crystallization of progesterone polymorphs using polymer-induced heteronucleation (PIHn) method

Progesterone is a natural hormone steroid used in humans for several treatments and in livestock for artificial insemination, which exhibits two polymorphic forms at ambient conditions: form 1 and form 2. Form 2 is metastable and more soluble than form 1; however, it is not suitable to use as powder raw material because it transforms into form 1 by the effects of grinding. A polymorphic screening of progesterone based on polymer-induced heteronucleation method was performed as an alternative to prepare the metastable form. Polyvinyl alcohol, hydroxypropyl methylcellulose (HPMC), dextran, gelatin, polyisoprene (PI) and acrylonitrile-butadiene (NBR) copolymer were used. Crystals were prepared from 0.5, 10 and 40?mg/mL solutions in acetone at room temperature by solvent evaporation. The samples were characterized by X-ray powder diffraction, differential scanning calorimetry (DSC), scanning electron microcopy and attenuated total reflectance infrared Fourier transform spectroscopy. Form 1 was nucleated from 40?mg/mL solutions on the six polymers and from 10?mg/mL solutions on PI and NBR. The mixture of form 1 and form 2 was obtained from 10?mg/mL solution on HPMC, dextran and gelatin and from 0.5?mg/mL solution crystallizations. Therefore, the polymeric devices, which crystallized the metastable and more soluble polymorph (2) of progesterone, would be a promissory alternative for the pharmaceutical applications.     

A patient-specific computational model of hypoxia-modulated radiation resistance in glioblastoma using 18F-FMISO-PET

Glioblastoma multiforme (GBM) is a highly invasive primary brain tumour that has poor prognosis despite aggressive treatment. A hallmark of these tumours is diffuse invasion into the surrounding brain, necessitating a multi-modal treatment approach, including surgery, radiation and chemotherapy. We have previously demonstrated the ability of our model to predict radiographic response immediately following radiation therapy in individual GBM patients using a simplified geometry of the brain and theoretical radiation dose. Using only two pre-treatment magnetic resonance imaging scans, we calculate net rates of proliferation and invasion as well as radiation sensitivity for a patient''s disease. Here, we present the application of our clinically targeted modelling approach to a single glioblastoma patient as a demonstration of our method. We apply our model in the full three-dimensional architecture of the brain to quantify the effects of regional resistance to radiation owing to hypoxia in vivo determined by [¹⁸F]-fluoromisonidazole positron emission tomography (FMISO-PET) and the patient-specific three-dimensional radiation treatment plan. Incorporation of hypoxia into our model with FMISO-PET increases the model–data agreement by an order of magnitude. This improvement was robust to our definition of hypoxia or the degree of radiation resistance quantified with the FMISO-PET image and our computational model, respectively. This work demonstrates a useful application of patient-specific modelling in personalized medicine and how mathematical modelling has the potential to unify multi-modality imaging and radiation treatment planning.     

Amino‐polyvinyl Alcohol Coated Superparamagnetic Iron Oxide Nanoparticles are Suitable for Monitoring of Human Mesenchymal Stromal Cells In Vivo

Mesenchymal stromal cells (MSCs) are promising candidates in regenerative cell‐therapies. However, optimizing their number and route of delivery remains a critical issue, which can be addressed by monitoring the MSCs’ bio‐distribution in vivo using super‐paramagnetic iron‐oxide nanoparticles (SPIONs). In this study, amino‐polyvinyl alcohol coated (A‐PVA) SPIONs are introduced for cell‐labeling and visualization by magnetic resonance imaging (MRI) of human MSCs. Size and surface charge of A‐PVA‐SPIONs differ depending on their solvent. Under MSC‐labeling conditions, A‐PVA‐SPIONs have a hydrodynamic diameter of 42 ± 2 nm and a negative Zeta potential of 25 ± 5 mV, which enable efficient internalization by MSCs without the need to use transfection agents. Transmission X‐ray microscopy localizes A‐PVA‐SPIONs in intracellular vesicles and as cytosolic single particles. After identifying non‐interfering cell‐assays and determining the delivered and cellular dose, in addition to the administered dose, A‐PVA‐SPIONs are found to be non‐toxic to MSCs and non‐destructive towards their multi‐lineage differentiation potential. Surprisingly, MSC migration is increased. In MRI, A‐PVA‐SPION‐labeled MSCs are successfully visualized in vitro and in vivo. In conclusion, A‐PVA‐SPIONs have no unfavorable influences on MSCs, although it becomes evident how sensitive their functional behavior is towards SPION‐labeling. And A‐PVA‐SPIONs allow MSC‐monitoring in vivo.     

Unraveling the Dynamic Nanoscale Reducibility (Ce4+ → Ce3+) of CeOx–Ru in Hydrogen Activation

The interaction of molecular hydrogen with ceria is of important relevance for heterogeneous catalysis related to green chemistry and renewable energy. Here, the complex structural transformations of a well‐defined cerium oxide model catalyst are followed in situ and in real time when exposed to a reactive H₂ environment. By using electron spectromicroscopy and diffraction with chemical and structural sensitivities, it is demonstrated that the transition from CeO₂ to crystalline Ce₂O₃ occurs through a mixture of transient, coexisting phases on the nanoscale. The findings establish a clear relationship between structure and functionality for hydrogen dissociation over ceria(111), bearing profound implications on the nature of the reduction (Ce⁴⁺ → Ce³⁺) and mechanism for H₂ scission.     

Development of an Active Thermoplastic Film with Oxygen Scavengers Made of Activated Carbon and Sodium Erythorbate

An active thermoplastic film made of low‐density polyethylene (LDPE) filled with oxygen scavengers made of powdered activated carbon (PAC) impregnated with sodium erythorbate (SE) was developed for packaging applications. Initial tests indicated that the impregnation of PAC with SE enhanced the heat resistance of SE, thereby allowing processing at temperatures typical of LDPE manufacturing. Subsequently, LDPE films with PAC/SE particles were manufactured in coupons that represented a typical juice package, and experiments indicated that these films absorbed 3.57 mg of oxygen in 11 days. This amount corresponded to 80% the concentration of oxygen in the headspace of the package. Furthermore, findings indicated that active particles alone have 10 times higher oxygen absorption capacity than the active LDPE film. Finally, the physical properties of the film were characterized by microscopy where oxygen scavengers showed a good dispersion within the matrix. However, 20 wt.% of these active particles decreased tensile strength of the film by 53%. Copyright © 2014 John Wiley & Sons, Ltd.