Exquisite integration of quality-by-design and green analytical approaches for simultaneous determination of xylometazoline and antazoline in eye drops and rabbit aqueous humor, application to stability study.

This work implements a stability indicating HPLC method developed to simultaneously determine xylometazoline (XYLO) and antazoline (ANT) in their binary mixture, rabbit aqueous humor and cited drug's degradates by applying analytical quality-by-design (AQbD) combined with green analytical chemistry (GAC) experiment for the first time. This integration was designed to maximize efficiency and minimize environmental impacts, as well as energy and solvent consumption. Analytical quality-by-design was applied to achieve our aim starting with evaluation of quality risk and scouting analysis, tracked via five parameters chromatographic screening using Placket-Burman design namely: pH, temperature, organic solvent percentage, flow rate, and wavelength detection. Recognizing the critical method parameters was done followed by optimization employing central composite design and Derringer's desirability toward assess optimum conditions that attained best resolution with satisfactory peak symmetry with short run time. Optimal chromatographic separation was attained by means of an XBridge® C18 (4.6 × 250 mm, 5 µm) column through isocratic elution using a mobile phase consists of phosphate buffer (pH 3.0): ethanol (60:40, by volume) at a 1.6 mL/min flow rate and 230.0 nm UV detection. Linearity acquired over a concentration range of 1.0-100.0 µg/mL and 0.5-100.0 µg/mL for XYLO and ANT, respectively. Furthermore, imperiling cited drugs' stock solutions to stress various conditions and satisfactory peaks of degradation products were obtained indicating that cited drugs are vulnerable to oxidative degradation and basic hydrolysis. Degradates' structures were elucidated using mass spectrometry. Applying various assessment tools; namely: analytical greenness (AGREE), green analytical procedure index (GAPI), analytical eco-scale, and national environmental method index (NEMI), Greenness method's evaluation was applied and proved to be green. In fact, the developed method is established to be perceptive, accurate, and selective to assess cited drugs for routine analysis.

Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres.

This study deals with the process of optimization and synthesis of Poly(3-hydroxybutyrate) microspheres with encapsulated Cl-amidine. Cl-amidine is an inhibitor of peptidylarginine deiminases (PADs), a group of calcium-dependent enzymes, which play critical roles in a number of pathologies, including autoimmune and neurodegenerative diseases, as well as cancer. While Cl-amidine application has been assessed in a number of in vitro and in vivo models; methods of controlled release delivery remain to be investigated. P(3HB) microspheres have proven to be an effective delivery system for several compounds applied in antimicrobial, wound healing, cancer, and cardiovascular and regenerative disease models. In the current study, P(3HB) microspheres with encapsulated Cl-amidine were produced in a size ranging from ~4-5 µm and characterized for surface morphology, porosity, hydrophobicity and protein adsorption, in comparison with empty P(3HB) microspheres. Cl-amidine encapsulation in P(3HB) microspheres was optimized, and these were found to be less hydrophobic, compared with the empty microspheres, and subsequently adsorbed a lower amount of protein on their surface. The release kinetics of Cl-amidine from the microspheres were assessed in vitro and expressed as a function of encapsulation efficiency. There was a burst release of ~50% Cl-amidine in the first 24 h and a zero order release from that point up to 16 days, at which time point ~93% of the drug had been released. As Cl-amidine has been associated with anti-cancer effects, the Cl-amidine encapsulated microspheres were assessed for the inhibition of vascular endothelial growth factor (VEGF) expression in the mammalian breast cancer cell line SK-BR-3, including in the presence of the anti-proliferative drug rapamycin. The cytotoxicity of the combinatorial effect of rapamycin with Cl-amidine encapsulated P(3HB) microspheres was found to be 3.5% more effective within a 24 h period. The cells treated with Cl-amidine encapsulated microspheres alone, were found to have 36.5% reduction in VEGF expression when compared with untreated SK-BR-3 cells. This indicates that controlled release of Cl-amidine from P(3HB) microspheres may be effective in anti-cancer treatment, including in synergy with chemotherapeutic agents. Using controlled drug-delivery of Cl-amidine encapsulated in Poly(3-hydroxybutyrate) microspheres may be a promising novel strategy for application in PAD-associated pathologies.

Modifications of Polymers through the Addition of Ultraviolet Absorbers to Reduce the Aging Effect of Accelerated and Natural Irradiation.

The photooxidative degradation process of plastics caused by ultraviolet irradiation leads to bond breaking, crosslinking, the elimination of volatiles, formation of free radicals, and decreases in weight and molecular weight. Photodegradation deteriorates both the mechanical and physical properties of plastics and affects their predicted life use, in particular for applications in harsh environments. Plastics have many benefits, while on the other hand, they have numerous disadvantages, such as photodegradation and photooxidation in harsh environments and the release of toxic substances due to the leaching of some components, which have a negative effect on living organisms. Therefore, attention is paid to the design and use of safe, plastic, ultraviolet stabilizers that do not pose a danger to the environment if released. Plastic ultraviolet photostabilizers act as efficient light screeners (absorbers or pigments), excited-state deactivators (quenchers), hydroperoxide decomposers, and radical scavengers. Ultraviolet absorbers are cheap to produce, can be used in low concentrations, mix well with polymers to produce a homogenous matrix, and do not alter the color of polymers. Recently, polyphosphates, Schiff bases, and organometallic complexes were synthesized and used as potential ultraviolet absorbers for polymeric materials. They reduced the damage caused by accelerated and natural ultraviolet aging, which was confirmed by inspecting the surface morphology of irradiated polymeric films. For example, atomic force microscopy revealed that the roughness factor of polymers' irradiated surfaces was improved significantly in the presence of ultraviolet absorbers. In addition, the investigation of the surface of irradiated polymers using scanning electron microscopy showed a high degree of homogeneity and the appearance of pores that were different in size and shape. The current work surveys for the first time the use of newly synthesized, ultraviolet absorbers as additives to enhance the photostability of polymeric materials and, in particular, polyvinyl chloride and polystyrene, based mainly on our own recent work in the field.

Synchronous UPLC Resolution of Aceclofenac and Diacerin in Their Powdered Forms and Matrix Formulation: Stability Study.

Accurate, rapid and selective reversed phase ultra-performance liquid chromatography method with UV detection has been established and validated for the synchronous determination of aceclofenac (ACE) and diacerin (DIA) in the occurrence of diclofenac sodium and rhein, their main degradation products, respectively. Chromatographic separation was accomplished using Inertsil C-18 column (50 × 2.1 mm i.d., 1.7 µm particle size) in isocratic mode, with mobile phase consisting of 20 mM ammonium acetate buffer:acetonitrile in the ratio of 42:58 (v/v), pH adjusted to 3.00 by using 10% acetic acid, the flow rate of 0.25 mL/min and UV detection was performed at 265 nm. The retention times were 2.00 +/- 0.24, 2.69 +/- 0.19, 4.00 +/- 0.23 and 5.24 +/- 0.25 min for DIA, rhein, ACE and diclofenac sodium, respectively. Excellent linearity was shown over a range of 1.0-150.0 µg/mL and 0.5-87.5 µg/mL with mean percentage recoveries of 98.87 ± 1.19 and 98.84 ± 1.08 for ACE and DIA, respectively. Parameters of precision and accuracy of the method meet the established criteria. The obtained RSD values were quite low and indicate good reproducibility of the method. Thus, the developed method can be used for the combined dosage form analysis and its chemical stability studies.

Influence of Polyphosphates on the Physicochemical Properties of Poly (Vinyl Chloride) after Irradiation with Ultraviolet Light.

Three new polyphosphates were synthesized in good yields by reacting diethylenetriamine with the appropriate phosphate ester in ethanol under acidic conditions. The polyphosphate structures were determined using FT-IR and 1H-NMR spectroscopies, and their elemental compositions were confirmed by EDX spectroscopy. Polyphosphates were added to poly(vinyl chloride) (PVC) at low concentrations to fabricate thin films. The PVC films were irradiated with ultraviolet light for long periods, and the effect of polyphosphates as the photostabilizer was investigated by determining changes in the infrared spectra (intensity of specific functional group peaks), reduction in molecular weight, weight loss, and surface morphology. Minimal changes were seen for PVC films containing polyphosphate compared to that for the blank film. In addition, optical, scanning electron, and atomic force microscopies were used to inspect the surface morphology of films. Undesirable changes due to photodegradation were negligible in PVC films containing additives compared to films containing no additives. In addition, the surfaces were smoother and more homogeneous. Polyphosphates, and in particular ones that contain an ortho-geometry, act as efficient photostabilizers to reduce the rate of photodegradation. Polyphosphates absorb ultraviolet light, chelate with polymeric chains, scavenge radical moieties, and decompose peroxide residues.

Treatment Outcome of 227 Patients with Sinonasal Adenoid Cystic Carcinoma (ACC) after Intensity Modulated Radiotherapy and Active Raster-Scanning Carbon Ion Boost: A 10-Year Single-Center Experience.

We aimed to evaluate the treatment outcome of primary and postoperative bimodal radiotherapy (RT) including intensity modulated photon radiotherapy (IMRT) and carbon ion radiotherapy (CIRT) for sinonasal adenoid cystic carcinoma (ACC) patients. Medical records of 227 consecutive patients who received either a primary (n = 90, 40%) or postoperative (n = 137, 60%; R2, n = 86, 63%) IMRT with doses between 48 and 56 Gy in 1.8 or 2 Gy fractions and active raster-scanning carbon ion boost with 18 to 24 Gy (RBE, relative biological effectiveness) in 3 Gy (RBE) fractions between 2009 and 2019 up to a median total dose of 80 Gy (EQD2, equivalent dose in 2 Gy single dose fractions, range 71-80 Gy) were reviewed. Results: Median follow-up was 50 months. In univariate and multivariate analysis, no significant difference in local control (LC) could be shown between the two treatment groups (p = 0.33). Corresponding 3-year LC rates were 79% for primary bimodal RT and 82% for postoperative bimodal RT, respectively. T4 stage (p = 0.002) and solid histology (p = 0.005) were identified as independent prognostic factors for decreased LC. Significant worse long-term treatment tolerance was observed for postoperatively irradiated patients with 17% vs. 6% late grade 3 toxicity (p < 0.001). Primary radiotherapy including IMRT and carbon ion boost for dose-escalation results in adequate LC with less long-term grade 3 toxicity compared to postoperative bimodal radiotherapy in sinonasal ACC patients. The high rate of macroscopic tumor disease in the postoperative group makes the interpretation of the beneficial results in LC for primary RT difficult.

Results of a combination treatment with intensity modulated radiotherapy and active raster-scanning carbon ion boost for adenoid cystic carcinoma of the minor salivary glands of the nasopharynx.

OBJECTIVES: We aimed to present the first clinical results for adenoid cystic carcinoma (ACC) of the nasopharynx after primary radiotherapy (RT) with the focus on local control (LC) and patterns of recurrence. MATERIALS AND METHODS: We retrospectively analyzed 59 patients with ACC of the nasopharynx, who were treated with bimodal radiotherapy (RT) consisting of intensity modulated radiotherapy and carbon ion boost at the Heidelberg Ion-Beam Therapy Center between 2009 and 2018. The patients had predominantly inoperable (n = 42, 72%) or incompletely resected (n = 17, 29%) tumors. Kaplan-Meier estimates and the log-rank (Mantel-Cox) test were used for univariate and multivariate analyses. RESULTS: The median follow-up was 32 months. At last follow-up, 67% of the patients were still alive (n = 39/58), of whom 74% were free of progression (n = 29/39). The 2-year LC, distant progression-free survival (DPFS) and overall survival (OS) were 83%, 81%, 87% and the estimated 5-year LC, DPFS and OS were 49%, 54%, 69%, respectively. LC was significantly inferior in patients with large tumor volumes (gross tumor volume, GTV > 100 cc, p = 0.020) and T4 tumors (p = 0.021). The majority of the recurrences occurred at the margin, where critical structures were spared (n = 11/19, 58%). Overall, grade 3 toxicity was moderate with 12% acute and 8% late side effects. CONCLUSION: Bimodal RT including active raster-scanning carbon ion boost for nasopharyngeal ACC resulted in adequate LC and OS rates with moderate toxicity. T4 stage, large tumor volume and the necessary dose sparing in critical structures, i.e. optic nerves, brain stem and orbit, negatively affected LC.

The effect of high UV radiation exposure environment on the novel PVC polymers.

Although plastic induces environmental damages, almost the consumption of poly(vinyl chloride) never stops increasing. Therefore, this work abstracted by two parts, first, synthesis of Schiff bases 1-4 compounds through the reaction of amino group with appropriate aromatic aldehyde, reaction of PVC with Schiff bases compounds 1-4 in THF to form a new modified PVC-1, PVC-2, PVC-3, and PVC-4. The structures of Schiff bases 1-4 and the modified PVC-1, PVC-2, PVC-3, and PVC-4 have been characterized by different spectroscopic analyses. Second, the influence of introducing 4-amino-1,2,4-triazole as a pendent groups into PVC chain investigated on photostability rules of tests. The modified polymers photostability investigated by observing indices (ICO, Ipo, and IOH), weight loss, UV and morphological studies, and all results obtained indicated that PVC-1, PVC-2, PVC-3 and PVC-4 gave lower growth rate of ICO, IPO, and IOH through UV exposure time. The photostability are given as PVC-4 < PVC-3 < PVC-2 < PVC-1 from different mechanisms which suggested building on existence of 4-amino-1,2,4-triazole moieties in the polymer chain.

Fabrication of ordered honeycomb porous poly(vinyl chloride) thin film doped with a Schiff base and nickel(II) chloride.

A modified poly(vinyl chloride) honeycomb thin film containing a low concentration of a thiadiazole Schiff base and nickel(II) chloride was successfully fabricated using the casting process. The surface morphology of the synthesized thin film was investigated using the scanning electronic microscopy. The synthesized poly(vinyl chloride) thin film was found to have a homogeneous surface morphology with a high crystalline nature. The addition of nickel(II) chloride was discovered to be vital for the formation of the honeycomb like structure.

Serum Soluble Interleukin 2 Receptor Level as a Marker of Acute Rejection in Pediatric Kidney Transplant Recipients.

BACKGROUND: Despite advances in immunosuppression, acute allograft rejection remains one of the key factors affecting patient and graft survival in pediatric kidney transplantation. The aim of the study is to evaluate the role of serum soluble IL2 receptor (sIL2R) level as a noninvasive assessment parameter of acute rejection (AR). METHOD: Serum sIL2R level was measured (using enzyme-linked immune-sorbent assay technique) in 60 pediatric kidney transplant recipients (30 recipients with AR and 30 transplant recipients with stable graft function). RESULTS: The mean values of sIL2R level in patients experiencing AR (14.8 ± 6.54) ng/mL were significantly higher than that in patients with stable graft functions (6.44 ±1.95) ng/mL (p = 0.0001). In addition; patients with AR proved by graft biopsy had their mean values of sIL2R level (16.19 ± 7.48) ng/mL significantly higher than that of other recipients in the study population (p = 0.032). CONCLUSION: Serum sIL2R level may serve as a noninvasive diagnostic indicator in pediatric kidney transplant recipients experiencing AR.

SEM analysis of the tunable honeycomb structure of irradiated poly(vinyl chloride) films doped with polyphosphate.

The fabrication of tunable poly(vinyl chloride) porous films containing polyphosphate as an additive was successful. Irradiation of poly(vinyl chloride) films containing polyphosphate at a low concentration (0.5% by weight) with an ultraviolet light (λmax = 313 nm) for 300 h leads to the formation of a honeycomb like structure. The scanning electron microscopy images, at different magnification power, confirmed the production of the PVC honeycomb-like structure. The morphological images of the polymeric film showed a rough surface and a large number of regularly distributed hexagonal pores. The number of pores increased upon irradiation time and it was maximum after 300 h. The honeycomb structure formation could be due to the regular aggregation of polyphosphate among the polymeric chains, the increase in solution intrinsic viscosity and evaluation of hydrogen chloride gas through dehydrochlorination process.

Polyphosphates as Inhibitors for Poly(vinyl Chloride) Photodegradation.

Three polyphosphates were used as inhibitors for poly(vinyl chloride) (PVC) photodegradation. The polyphosphates were added to PVC at a concentration of 0.5% by weight. The PVC films (40 µm thickness) were irradiated at room temperature with ultraviolet (UV) light for up to 300 h. The changes in PVC films after irradiation were monitored by Fourier transform infrared spectroscopy, weight loss, viscosity-average molecular weight determination, and atomic force microscopy. These changes were very noticeable in the blank PVC films compared to the ones obtained when additives were used. The polyphosphates can inhibit the PVC photodegradation through direct absorption of UV light, interactions with PVC chains, and acting as radical scavengers.

New Eco-Friendly Phosphorus Organic Polymers as Gas Storage Media.

Three phosphate esters 1⁻3 were successfully synthesized from the reaction of 2-, 3- and 4-hydroxybenzaldehyde with phosphoryl chloride. Reactions of 1⁻3 with benzidine in the presence of glacial acetic acid gave the corresponding novel phosphorus organic polymers 4⁻6 containing the azomethane linkage. The structures of the synthesized compounds were confirmed by Fourier transform infrared spectroscopy, nuclear magnetic resonance and elemental analysis. Interesting physiochemical properties for the polymeric materials 4⁻6 were observed using a combination of several techniques such as gel permeation chromatography, scanning electron microscopy, Brunauer⁻Emmett⁻Teller and nitrogen adsorption⁻desorption isotherm, Barrett⁻Joyner⁻Halenda and H-sorb 2600 analyzer. The mesoporous polymers 4⁻6 exhibit tunable porosity with Brunauer⁻Emmett⁻Teller surface area (SABET = 24.8⁻30 m²·g⁻1), pore volume (0.03⁻0.05 cm³·g⁻1) and narrow pore size distribution, in which the average pore size was 2.4⁻2.8 nm. Polymers 4⁻6 were found to have high gas storage capacity and physico-chemical stability, particularly at a high pressure. At 323 K and 50 bars, polymers 4⁻6 have remarkable carbon dioxide uptake (up to 82.1 cm³·g⁻1) and a low hydrogen uptake (up to 7.4 cm³·g⁻1). The adsorption capacity of gasses for polymer 5 was found to be higher than those for polymers 4 and 6.

Role of serum anti-C1q antibodies as a biomarker for nephritis activity in pediatric and adolescent Egyptian female patients with SLE.

OBJECTIVE: To evaluate serum anti-C1q antibodies as a biomarker of systemic lupus erythematosus (SLE) flare and as a proposed noninvasive alternative to renal biopsy which is still the "gold standard" to determine renal activity in SLE. METHODS: Serum anti-C1q antibodies were measured in our patients (all were females), they were followed at the nephrology and pediatric nephrology units at the Faculties of Medicine of Cairo University and Misr University for science and technology (MUST). Our study included 120 patients in the pediatric and adolescent age group and they were categorized into three groups with (mean ± SD of 16.7 ± 3, 16.1 ± 2, 15.9 ± 3) respectively: Group 1 including 40 patients with SLE and active lupus nephritis; Group 2 including 40 patients with SLE and without active lupus nephritis, but with some extra renal activity mainly arthritis; and Group 3 including 40 healthy subjects. RESULTS: Anti-C1q antibodies were found to be significantly higher in patients with active lupus nephritis than those without active nephritis than control individuals with a median (range) of [27.5 (14 - 83), 9 (2.5 - 30), 7 (2 - 13)] respectively. In those with active lupus nephritis, anti-C1q was found to correlate significantly with other parameters assessing lupus nephritis activity like C3 (r = -0.33, p < 0.04), C4 (r = -0.32, p < 0.044), daily urinary protein excretion (r = 0.32, p < 0.036), renal SLEDAI (r = 0.64, p < 0.001), and activity index (r = 0.71, p < 0.001). CONCLUSIONS: Anti-C1q antibodies can be used as a considerable marker for LN activity in that age group with 97.5% sensitivity and 65% specificity with the cutoff level 12 U/l. These levels are clearly higher than those for traditional markers of disease activity such as C3/C4 consumption and anti-dsDNA.