Destruction of dimethyl ether and methyl formate by collisions with He+^+

To correctly model the abundances of interstellar complex organic molecules (iCOMS) in different environments, both formation and destruction routes should be appropriately accounted for. While several scenarios have been explored for the formation of iCOMs via grain and gas-phase processes, much less work has been devoted to understanding the relevant destruction pathways, with special reference to (dissociative) charge exchange or proton transfer reactions with abundant atomic and molecular ions such as He$^+$, H$_3^+$ and HCO$^+$. By using a combined experimental and theoretical methodology we provide new values for the rate coefficients and branching ratios (BRs) of the reactions of He$^+$ ions with two important iCOMs, namely dimethyl ether (DME) and methyl formate (MF). We also review the destruction routes of DME and MF by other two abundant ions, namely H$_3^+$ and HCO$^+$. Based on our recent laboratory measurements of cross sections and BRs for the DME/MF + He$^+$ reactions over a wide collision energy range, we extend our theoretical insights on the selectivity of the microscopic dynamics to calculate the rate coefficients $k(T)$ in the temperature range from 10 to 298 K. We implement these new and revised kinetic data in a general model of cold and warm gas, simulating environments where DME and MF have been detected. Due to stereodynamical effects present at low collision energies, the rate coefficients, BRs and temperature dependences here proposed differ substantially from those reported in KIDA and UDfA, two of the most widely used astrochemical databases. These revised rates impact the predicted abundances of DME and MF, with variations up to 40% in cold gases and physical conditions similar to those present in prestellar coresComment: accepted for publication in Astronomy and Astrophysics (manuscript no. AA/2018/34585), 10 pages, 3 figure

Apoferritin nanocage as drug reservoir: is it a reliable drug delivery system?

Apoferritin is a complex protein with a number of possibilities for drug delivery and drug targeting technologies, as it could be considered as the future self-assembling, not-toxic protein drug delivery carrier. Few years ago, this concept was a reality; nowadays, after more than 10 years of research, a clear painting of Apoferritin, loaded with drugs, is lacking, in terms of protocols of formulation, characterization, drug release and application. Therefore, a critical evaluation and overall understanding of Apoferritin is due to speed up the possibilities for its translatability into clinical application

Protein cage nanostructure as drug delivery system: magnifying glass on apoferritin

New frontiers in nanomedicine are moving towards the research of new biomaterials. Apoferritin (APO), is a uniform regular self-assemblies nano-sized protein with excellent biocompatibility and a unique structure that affords it the ability to stabilize small active molecules in its inner core. Areas covered: APO can be loaded by applying a passive process (mainly used for ions and metals) or by a unique formulative approach based on disassemby/reassembly process. In this article, we aim to organize the experimental evidence provided by a number of studies on the loading, release and targeting. Attention is initially focused on the most investigated antineoplastic drug and contrast agents up to the most recent application in gene therapy. Expert opinion: Various preclinical studies have demonstrated that APO improved the potency and selectivity of some chemotherapeutics. However, in order to translate the use of APO into therapy, some issues must be solved, especially regarding the reproducibility of the loading protocol used, the optimization of nanocarrier characterization, detailed understanding of the final structure of loaded APO, and the real mechanism and timing of drug release

Potential Use of Nanomedicine for Drug Delivery Across the Blood-Brain Barrier in Healthy and Diseased Brain

The research of efficacious non-invasive therapies for the treatment of brain diseases represents a huge challenge, as people affected by disorders of the central nervous system (CNS) will significantly increase. Moreover, the blood-brain barrier is a key factor in hampering a number of effective drugs to reach the CNS. This review is therefore focusing on possible interventions of nanomedicine-based approaches in selected diseases affecting the CNS. A wide overview of the most outstanding results on preclinical evaluations of the potential of nanomedicine in brain diseases (i.e. brain tumor, Alzheimer, Parkinson, epilepsy and others) is given, with highlights on the data with relevant interest and real possibility in translation from bench-to-bedside. Moreover, a critical evaluation on the rationale in planning nanosystems to target specific brain pathologies is described, opening the path to a more structured and pathology-tailored design of nanocarriers

Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome

Context/Objective: Current diagnostic criteria for polycystic ovary syndrome (PCOS) have generated distinct PCOS phenotypes, based on the different combinations of diagnostic features found in each patient. Our aim was to assess whether either each single diagnostic feature or their combinations into the PCOS phenotypes may predict insulin resistance in these women. Patients/Design: A total of 137 consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of diagnostic and metabolic features. Insulin sensitivity was measured by the glucose clamp technique. Results: Among women with PCOS, 84.7% had hyperandrogenism, 84.7% had chronic oligoanovulation, and 89% had polycystic ovaries. According to the individual combinations of these features, 69.4% of women had the classic phenotype, 15.3% had the ovulatory phenotype, and 15.3% had the normoandrogenic phenotype. Most subjects (71.4%) were insulin resistant. However, insulin resistance frequency differed among phenotypes, being 80.4%, 65.0%, and 38.1%, respectively, in the 3 subgroups (P < .001). Although none of the PCOS diagnostic features per se was associated with the impairment in insulin action, after adjustment for covariates, the classic phenotype and, to a lesser extent, the ovulatory phenotype were independently associated with insulin resistance, whereas the normoandrogenic phenotype was not. Metabolic syndrome frequency was also different among phenotypes (P = .030). Conclusions: There is a scale of metabolic risk among women with PCOS. Although no single diagnostic features of PCOS are independently associated with insulin resistance, their combinations, which define PCOS phenotypes, may allow physicians to establish which women should undergo metabolic screening. In metabolic terms, women belonging to the normoandrogenic phenotype behave as a separate group

AFM, ESEM, TEM, and CLSM in liposomal characterization: a comparative study

An outstanding aspect of pharmaceutical nanotechnology lies in the characterization of nanocarriers for targeting of drugs and other bioactive agents. The development of microscopic techniques has made the study of the surface and systems architecture more attractive. In the field of pharmaceutical nanosystems, researchers have collected vital information on size, stability, and bilayer organization through the microscopic characterization of liposomes. This paper aims to compare the results obtained by atomic force microscopy, environmental scanning electron microscopy, transmission electron microscopy, and confocal laser scanning microscopy to point out the limits and advantages of these applications in the evaluation of vesicular systems. Besides this comparative aim, our work proposes a simple confocal laser scanning microscopy procedure to rapidly and easily detect the liposomal membrane

Nanoparticle transport across the blood brain barrier

ABSTRACT: While the role of the blood-brain barrier (BBB) is increasingly recognized in the (development of treatments targeting neurodegenerative disorders, to date, few strategies exist that enable drug delivery of non-BBB crossing molecules directly to their site of action, the brain. However, the recent advent of Nanomedicines may provide a potent tool to implement CNS targeted delivery of active compounds. Approaches for BBB crossing are deeply investigated in relation to the pathology: among the main important diseases of the CNS, this review focuses on the application of nanomedicines to neurodegenerative disorders (Alzheimer, Parkinson and Huntington's Disease) and to other brain pathologies as epilepsy, infectious diseases, multiple sclerosis, lysosomal storage disorders, strokes

Current Strategies for the Delivery of Therapeutic Proteins and Enzymes to Treat Brain Disorders

Brain diseases and injuries are growing to be one of the most deadly and costly medical conditions in the world. Unfortunately, current treatments are incapable of ameliorating the symptoms let alone curing the diseases. Many brain diseases have been linked to a loss of function in a protein or enzyme, increasing research for improving their delivery. This is no easy task due to the delicate nature of proteins and enzymes in biological conditions, as well as the many barriers that exist in the body ranging from those in circulation to the more specific barriers to enter the brain. Several main techniques are being used (physical delivery, protein/enzyme conjugates, and nanoparticle delivery) to overcome these barriers and create new therapeutics. This review will cover recently published data and highlights the benefits and deficits of possible new protein or enzyme therapeutics for brain diseases

Apoferritin nanocage as streptomycin drug reservoir: Technological optimization of a new drug delivery system

The aim of this study is to formulate and characterize streptomycin-loaded apoferritin nanoparticles (ApoStrep NPs) for their potential therapeutic use in bacterial resistant infections (i.e. tuberculosis). ApoStrep NPs were prepared by disassembly/reassembly process via pH method and changing apoferritin/drug molar ratio, purified by dialyses process also associated with gel filtration chromatography and characterized in their chemico-physical and technological parameters as yield, size distribution, polidispersivity, morphology, internal structure, zeta potential and loading efficacy. The results showed that spherical reproducible NPs could be obtained by using apoferritin/drug molar ratio lower than 1:25 and purification based on the combination of dialysis and gel filtration chromatography. Photon correlation spectroscopy, Uv–visible detection and electron microscopy showed the maintenance of the native apoferritin chemico-physical properties and structure. When formulated with apoferritin/drug 1:10 and 1:25 molar ratio, ApoStrep NPs showed remarkable encapsulation efficacy (35% and 28%, respectively) along with kinetic profile of drug delivery, approximately 15% at 37 °C in 72 h, as evidenced by “in vitro” release experiments