A novel approach for skin infections: Controlled release topical mats of poly (lactic acid)/poly(ethylene succinate) blends containing Voriconazole

WOS: 000438500700010The oral and injectable formulations of Voriconazole (VRZ), a known antifungal agent with low solubility, seem to cause severe side effects. Consequently, topical application of VRZ could be advantageous for skin fungal infections. In this study, VRZ embedded in a polymeric matrix composed of biocompatible poly(lactic acid) (PLA) and poly(ethylene succinate) (PESu). The mats were prepared via solvent evaporation and fully characterized by Fourier-Transformed Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), in vitro hydrolysis and release studies. The prepared blends defined as immiscible by DSC and SEM while FTIR spectroscopy did not disclose noticeable interactions between the polymers. It was found that hydrolysis was improved by increasing PESu content into the blend. VRZ loaded blends spectra exhibit slight differentiation compared to neat blends while the absence of VRZ melting peak, as DSC illustrated, indicated drug amorphization. Lastly, in vitro release studies depicted a controlled release pattern dependent on mats' hydrolysis degree. An improved antifungal activity of mats was detected by disc diffusion method against various microorganisms. Ex vivo studies of VRZ did not determine high permeation while histopathology results using mice were profitable. The irritation experiments displayed that the mats did not induce any skin irritation

Optical Imaging of Surface Chemistry and Dynamics in Confinement

The interfacial structure and dynamics of water in a microscopically confined geometry is imaged in three dimensions and on millisecond time scales. We developed a 3D wide-field second harmonic microscope that employs structured illumination. We image pH induced chemical changes on the curved and confined inner and outer surfaces of a cylindrical glass micro-capillary immersed in aqueous solution. The image contrast reports on the orientational order of interfacial water, induced by charge-dipole interactions between water molecules and surface charges. The images constitute surface potential maps. Spatially resolved surface pKa,s values are determined for the silica deprotonation reaction. Values range from 2.3<pKa,s<10.7, highlighting the importance of surface heterogeneities. Water molecules that rotate along an oscillating external electric field are also imaged. With this approach, real time movies of surface processes that involve flow, heterogeneities and potentials can be made, which will further developments in electrochemistry, geology, catalysis, biology, and microtechnology

OLPT CONDUCTIVITY IN WOLLASTONITE INLAID NR/SBR TYPE ELASTOMER BASED MATERIAL

The electrical properties of wollastonite inlaid NR/SBR type elastomer based material have been evaluated. Electrical properties of the samples were measured in the temperature range of 303 to 453 K and the frequency range of 100 Hz – 40 MHz. All electrically measured parameters were given anomalies at 385 K. Only one type of dielectric relaxation process have been observed for all measurements. Physical parameters characterizing the dielectric behavior have been obtained by fitting the experimental results in the modified Debye equation. The activation energy which is thermally activated by dielectric relaxation process have been calculated to be 0.58 eV. DC conductivity increasing by temperature has been explained with the help of VFT model whereas the AC one has been clarified by the OLPT model

Protein and gene delivery systems for neurodegenerative disorders: Where do we stand today?

It has been estimated that every year, millions of people are affected by neurodegenerative disorders, which complicate their lives and their caregivers’ lives. To date, there has not been an approved pharmacological approach to provide the complete treatment of neurodegenerative disorders. The only available drugs may only relieve the symptoms or slow down the progression of the disease. The absence of any treatment is quite rational given that neurodegeneration occurs by the progressive loss of the function or structure of the nerve cells of the brain or the peripheral nervous system, which eventually leads to their death either by apoptosis or necrotic cell death. According to a recent study, even though adult brain cells are injured, they can revert to an embryonic state, which may help to restore their function. These interesting findings might open a new path for the development of more efficient therapeutic strategies to combat devastating neurodegenerative disorders. Gene and protein therapies have emerged as a rapidly growing field for various disorders, especially neurodegenerative diseases. Despite these promising therapies, the complete treatment of neurodegenerative disorders has not yet been achieved. Therefore, the aim of this review is to address the most up-to-date data for neurodegenerative diseases, but most importantly, to summarize the available delivery systems incorporating proteins, peptides, and genes that can potentially target such diseases and pass into the blood–brain barrier. The authors highlight the advancements, at present, on delivery based on the carrier, i.e., lipid, polymeric, and inorganic, as well as the recent studies on radiopharmaceutical theranostics

Ultrasensitive Label-Free Detection of Protein-Membrane Interaction Exemplified by Toxin-Liposome Insertion.

Measuring the high-affinity binding of proteins to liposome membranes remains a challenge. Here, we show an ultrasensitive and direct detection of protein binding to liposome membranes using high throughput second harmonic scattering (SHS). Perfringolysin O (PFO), a pore-forming toxin, with a highly membrane selective insertion into cholesterol-rich membranes is used. PFO inserts only into liposomes with a cholesterol concentration >30%. Twenty mole-percent cholesterol results in neither SHS-signal deviation nor pore formation as seen by cryo-electron microscopy of PFO and liposomes. PFO inserts into cholesterol-rich membranes of large unilamellar vesicles in an aqueous solution with Kd = (1.5 ± 0.2) × 10-12 M. Our results demonstrate a promising approach to probe protein-membrane interactions below sub-picomolar concentrations in a label-free and noninvasive manner on 3D systems. More importantly, the volume of protein sample is ultrasmall (<10 μL). These findings enable the detection of low-abundance proteins and their interaction with membranes

A novel index in healthy infants and children — subarachnoid space: ventricle ratio

Background: The subarachnoid space (SAS) and ventricular width (VW) in normalinfants and children were studied with ultrasonography to provide the objectivemeasurement and define a normal range for these measurements. The additional aim was to determine the stable ratio as a SAS/VW.Materials and methods: A total of 100 healthy subjects, including 48 males and52 females, were studied. The cases were divided into 3 age groups: 0–6 months(n = 65), 7–12 months (n = 24) and &gt; 13 months (n = 11). Transfontanel ultrasonography was performed in all the cases. SAS, VW and the SAS/VW ratios were calculated. The study was approved by the ethical committee. All parents wereinformed about the sonographic examination and their approvals were taken.Results: SAS was calculated as 3.1 (0.5–6) mm and VW was calculated as 3.6(1.3–5) mm. SAS/VW ratio was 0.9 ± 0.3. There was no statistically significant difference among SAS, VW and SAS/VW ratios in 3–97 percentile group (p &gt; 0.05).Conclusions: Ultrasonography can be used as a practicable and reproducible modalityin the measurement of SAS and VW in healthy children. It is a non-invasivemethod and allows for serial follow-up. SAS/VW ratio can be used as an index inhealthy children

Recent Advancements in Apoptosis-Based Therapeutic Approaches for Cancer Targeting

Apoptosis, known as programmed cell death, has been considered a potent target for the pharmacy industry. The scientific community has actively participated to research which evaluate active molecules for possible inhibition or induction of apoptosis. Nanocarriers especially for cancer targeting are widely found through literature; they mainly based on inorganic, lipid or polymer nanoparticles which incorporate anticancer drugs. Another important and innovative category of anticancer agents is that of microRNAs. In this chapter, a discussion about the most recent applications of apoptosis-based agents mainly focusing on cancer target is done

Probing the Hofmeister Effect with Ultrafast Core Hole Spectroscopy

In the current work, X-ray emission spectra of aqueous solutions of different inorganic salts within the Hofmeister series are presented. The results reflect the direct interaction of the ions with the water molecules and therefore, reveal general properties of the salt-water interactions. Within the experimental precision a significant effect of the ions on the water structure has been observed but no ordering according to the structure maker/structure breaker concept could be mirrored in the results indicating that the Hofmeister effect-if existent-may be caused by more complex interactions

Disordered Structural Ensembles of Vasopressin and Oxytocin and Their Mutants

Vasopressin and oxytocin are intrinsically disordered cyclic nonapeptides belonging to a family of neurohypophysial hormones. Although unique in their functions, these peptides differ only by two residues and both feature a tocin ring formed by the disulfide bridge between first and sixth cysteine residues. This sequence and structural similarity are experimentally linked to oxytocin agonism at vasopressin receptors and vasopressin antagonism at oxytocin receptors. Yet single- or double-residue mutations in both peptides have been shown to have drastic impacts on their activities at either receptor, and possibly the ability to bind to their neurophysin carrier protein. In this study we perform molecular dynamics simulations of the unbound native and mutant sequences of the oxytocin and vasopressin hormones to characterize their structural ensembles. We classify the subpopulations of these structural ensembles on the basis of the distributions of radius of gyration and secondary structure and hydrogen-bonding features of the canonical tocin ring and disordered tail region. We then relate the structural changes observed in the unbound form of the different hormone sequences to experimental information about peptide receptor binding, and more indirectly, carrier protein binding affinity, receptor activity, and protease degradation. This study supports the hypothesis that the structural characteristics of the unbound form of an IDP can be used to predict structural or functional preferences of its functional bound form

Mucinous cystic neoplasms of the mesentery: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site.</p> <p>Case presentation</p> <p>A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma.</p> <p>Methods and results</p> <p>We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors.</p> <p>Conclusion</p> <p>Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed.</p