Delivery of Poorly Soluble Drugs via Mesoporous Silica: Impact of Drug Overloading on Release and Thermal Profiles

Among the many methods available for solubility enhancement, mesoporous carriers are generating significant industrial interest. Owing to the spatial confinement of drug molecules within the mesopore network, low solubility crystalline drugs can be converted into their amorphous counterparts, which exhibit higher solubility. This work aims to understand the impact of drug overloading, i.e., above theoretical monolayer surface coverage, within mesoporous silica on the release behaviour and the thermal properties of loaded drugs. The study also looks at the inclusion of hypromellose acetate succinate (HPMCAS) to improve amorphisation. Various techniques including DSC, TGA, SEM, assay and dissolution were employed to investigate critical formulation factors of drug-loaded mesoporous silica prepared at drug loads of 100–300% of monolayer surface coverage, i.e., monolayer, double layer and triple layer coverage. A significant improvement in the dissolution of both Felodipine and Furosemide was obtained (96.4% and 96.2%, respectively). However, incomplete drug release was also observed at low drug load in both drugs, possibly due to a reversible adsorption to mesoporous silica. The addition of a polymeric precipitation inhibitor HPMCAS to mesoporous silica did not promote amorphisation. In fact, a partial coating of HPMCAS was observed on the exterior surface of mesoporous silica particles, which resulted in slower release for both drugs

The SYZ conjecture via homological mirror symmetry

These are expository notes based on a talk given at the Superschool on derived categories and D-branes at University of Alberta in July of 2016. The goal of these notes is to give a motivated introduction to the Strominger-Yau-Zaslow (SYZ) conjecture from the point of view of homological mirror symmetry.Comment: Contribution to the proceedings of the Superschool on derived categories and D-brane

Nickel Toxicity Interferes with NO3−/NH4+ Uptake and Nitrogen Metabolic Enzyme Activity in Rice (Oryza sativa L.)

The excessive use of nickel (Ni) in manufacturing and various industries has made Ni a serious pollutant in the past few decades. As a micronutrient, Ni is crucial for plant growth at low concentrations, but at higher concentrations, it can hamper growth. We evaluated the effects of Ni concentrations on nitrate (NO3−) and ammonium (NH4+) concentrations, and nitrogen metabolism enzyme activity in rice seedlings grown in hydroponic systems, using different Ni concentrations. A Ni concentration of 200 µM significantly decreased the NO3− concentration in rice leaves, as well as the activities of nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), and glutamate synthetase (GOGAT), respectively, when compared to the control. By contrast, the NH4 + concentration and glutamate dehydrogenase (GDH) activity both increased markedly by 48% and 46%, respectively, compared with the control. Furthermore, the activity of most active aminotransferases, including glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT), was inhibited by 48% and 36%, respectively, in comparison with the control. The results indicate that Ni toxicity causes the enzymes involved in N assimilation to desynchronize, ultimately negatively impacting the overall plant growth.This research was supported in part by National Key Research and Development Program (2018YFC1800305), Guangxi Major Special Project of Science and Technique (AA17202026-3), Hubei Special Project for Technique Innovation (2017ABA154), and Qatar University’s Vegetable Factory Project (QUEX–CAS–MJF–VF–18/19

Contribution of magnetic resonance imaging in the diagnosis of talus skip metastases of Ewing's sarcoma of the calcaneus in a child: a case report

<p>Abstract</p> <p>Introduction</p> <p>Ewing's sarcoma of the calcaneus is rare. About thirty cases with calcaneus involvement have been reported in the literature. Talus skip metastases have rarely been described in the available literature</p> <p>Case presentation</p> <p>We report a case of a 14-year-old Moroccan boy, who presented with Ewing's sarcoma of his right calcaneus, diagnosed by swelling of the calcaneus evolving over a year. Radiography, computed tomography and magnetic resonance imaging showed an important tumoral process of the calcaneus and talus skip metastases. The diagnosis was confirmed with histology after a biopsy. In spite of amputation and postoperative chemotherapy, our patient died six months later due to secondary respiratory distress after lung metastasis.</p> <p>Conclusion</p> <p>Imaging, especially magnetic resonance, is important in the diagnosis of Ewing sarcoma and skeletal skip metastases. Treatment of Ewing's sarcoma consists of chemotherapy, radiation therapy and surgical resection depending on the stage and extent of the disease. With the exception of lesions in the calcaneus, the prognosis for disease-free survival of Ewing's sarcoma of the foot is excellent.</p

Temporal Control over Transient Chemical Systems using Structurally Diverse Chemical Fuels

The next generation of adaptive, intelligent chemical systems will rely on a continuous supply of energy to maintain the functional state. Such systems will require chemical methodology that provides precise control over the energy dissipation process, and thus, the lifetime of the transiently activated function. This manuscript reports on the use of structurally diverse chemical fuels to control the lifetime of two different systems under dissipative conditions: transient signal generation and the transient formation of self-assembled aggregates. The energy stored in the fuels is dissipated at different rates by an enzyme, which in-stalls a dependence of the lifetime of the active system on the chemical structure of the fuel. In the case of transient signal generation, it is shown that different chemical fuels can be used to generate a vast range of signal profiles, allowing temporal control over two orders of magnitude. Regarding self-assembly under dissipative conditions, the ability to control the lifetime using different fuels turns out to be particularly important as stable aggregates are formed only at well-defined surfactant/fuel ratios, meaning that temporal control cannot be achieved by simply changing the fuel concentration

The most dangerous hospital or the most dangerous equation?

<p>Abstract</p> <p>Background</p> <p>Hospital mortality rates are one of the most frequently selected indicators for measuring the performance of NHS Trusts. A recent article in a national newspaper named the hospital with the highest or lowest mortality in the 2005/6 financial year; a report by the organization Dr Foster Intelligence provided information with regard to the performance of all NHS Trusts in England.</p> <p>Methods</p> <p>Basic statistical theory and computer simulations were used to explore the relationship between the variations in the performance of NHS Trusts and the sizes of the Trusts. Data of hospital standardised mortality ratio (HSMR) of 152 English NHS Trusts for 2005/6 were re-analysed.</p> <p>Results</p> <p>A close examination of the information reveals a pattern which is consistent with a statistical phenomenon, discovered by the French mathematician de Moivre nearly 300 years ago, described in every introductory statistics textbook: namely that variation in performance indicators is expected to be greater in small Trusts and smaller in large Trusts. From a statistical viewpoint, the number of deaths in a hospital is not in proportion to the size of the hospital, but is proportional to the square root of its size. Therefore, it is not surprising to note that small hospitals are more likely to occur at the top and the bottom of league tables, whilst mortality rates are independent of hospital sizes.</p> <p>Conclusion</p> <p>This statistical phenomenon needs to be taken into account in the comparison of hospital Trusts performance, especially with regard to policy decisions.</p

Intradermal vaccination with hollow microneedles: A comparative study of various protein antigen and adjuvant encapsulated nanoparticles

Drug Delivery TechnologySupramolecular & Biomaterials Chemistr