INVESTIGATION OF PRONIOSOMES GEL AS A PROMISING CARRIER FOR TRANSDERMAL DELIVERY OF GLIMEPIRIDE

Objectives: The aim of the study was to develop a proniosomal carrier system that is capable of efficiently delivering entrapped glimepiride over an extended period of time for the treatment of type 2 diabetes. Methods:  Proniosomal gels were developed based on span 60 with and without cholesterol. The entrapment efficiency of drug inside niosomes developed from hydration of the proniosomes gel was also characterized. The in vitro release and skin permeation of glimepiride from various proniosomes gel formulations were investigated. The stability studies were performed at 4°C and at room temperature. Results: The maximum entrapment efficiency was obtained when the cholesterol concentration was 10% of total lipid (90.02%). In vitro release through mixed cellulose ester membrane showed sustained release of drug from proniosomes gels. In vitro drug permeation across rabbit skin revealed improved drug permeation and higher transdermal flux with proniosomes gels compared to hydro-alcoholic gel of drug. Also, good physical stability was also achieved with proniosomes gels. Kinetics of in vitro skin permeation showed diffusion model of drug release from formulations. Conclusion: The study proved that the concentration of cholesterol had great influence on the properties of proniosomes gels. Hence, proniosomes preparation containing 10% cholesterol can significantly increase trans-epidermal flux and prolong the release of glimepiride.         Peer Review History: Article received on- 10 November   Revised on- 14 December       Accepted on- 16 December,  Available online 15 January 2017 Academic Editor: Dr. Asia Selman Abdullah, Al-Razi university, Department of Pharmacy, Yemen, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:        Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.5/10 Reviewer(s) detail: Dr. Heba M. Abd El-Azim, Damanhour University, Egypt, [email protected] Dr. Mohamed Derbali, Faculty of Pharmacy, Monastir, Tunisia, [email protected] Similar Articles: PREPARATION AND CHARACTERIZATION OF TOLTERODINE TARTRATE PRONIOSOME

High-Pressure Metal-Free Catalyzed One-Pot Two-Component Synthetic Approach for New 5-Arylazopyrazolo[3,4-b]Pyridine Derivatives

An appropriate and efficient Q-tube-assisted ammonium acetate-mediated protocol for the assembly of the hitherto unreported 5-arylazopyrazolo[3,4-b]pyridines was demonstrated. This methodology comprises the cyclocondensation reaction of 5-amino-2-phenyl-4H-pyrazol-3-one with an assortment of arylhydrazonals in an NH$_4$OAc/AcOH buffer solution operating a Q-tube reactor. This versatile protocol exhibited several outstanding merits: easy work-up, mild conditions, scalability, broad substrate scope, safety (the Q-tube kit is simply for pressing and sealing), and a high atom economy. Consequently, performing such reactions under elevated pressures and utilizing the Q-tube reactor seemed preferable for achieving the required products in comparison to the conventional conditions. Diverse spectroscopic methods and X-ray single-crystal techniques were applied to confirm the proposed structure of the targeted compounds

Reverse saturation absorption spectra and optical limiting properties of chlorinated tetrasubstituted phthalocyanines containing different metals

A highly non-aggregated series of peripherally tetra(2,6-diisopropylphenoxy) substituted phthalocyanines (Pcs) containing different metals (Al, Ga, In and Zn) were prepared and their nonlinear optical properties (NLO), including the optical limiting behavior were investigated. This study explores the effect of the implanted metals along with the peripheral chlorine atoms on the NLO of the prepared complexes, thereby improving their optical limiting performance. The best wavelength at which the Pc complex exhibits the strongest nonlinear effect was determined over the low absorption window region (420–590 nm) comprised between the Q and B bands using a nanosecond pulsed laser with the aid of a Z-scan technique. The excited state absorption cross sections (σeff) have been found to be wavelength dependent with common double peaks at 505 nm and around 485 nm and the highest value was calculated for Pc1–In (1.1 × 10−16 cm2). The figure of merit spectra show different spectral structure when compared to the excited state absorption spectra and the largest figure of merit value was found to be around 107 for Pc1–In derivative. In full agreement with reverse saturation results, the optical limiting measurements, carried out at 485 nm and 532 nm for each derivative, show very low optical limiting thresholds at the former wavelength. In the continuous wave excitation regime, the Z-scan measurements, which were carried out at 632.8 and 532 nm, showed strong refractive and absorptive nonlinear effects

Tetra and octa (2, 6-di-iso-propylphenoxy)-substituted phthalocyanines

This work reports on the synthesis of novel metal free, zinc, aluminum, gallium and indium tetra and octa (2,6-di-iso-propylphenoxy)-substituted phthalocyanine derivatives. UV-visible and 1H NMR analyses confirm that a non-planar conformation, adapted by the phenoxy substituents due to steric interaction in both derivative series, perfectly discourage cofacial aggregation. Fluorescence quantum yields vary as a function of the number of substituents on the ring periphery, while the fluorescence lifetimes display no distinct trend. Triplet quantum yields are significantly larger for the tetra 2,6-di-iso-propylphenoxy- substituted derivatives relative to their corresponding octa-substituted species. However there was no overall trend in the triplet lifetime values. For almost all of the phthalocyanine derivatives, singlet oxygen was produced with relatively good quantum yields. This study explores the possibility of fine-tuning their physicochemical properties by simple structural modification

Novel Pyridinium Based Ionic Liquid Promoter for Aqueous Knoevenagel Condensation: Green and Efficient Synthesis of New Derivatives with Their Anticancer Evaluation

Herein, a distinctive dihydroxy ionic liquid ([Py-2OH]OAc) was straightforwardly assembled from the sonication of pyridine with 2-chloropropane-1,3-diol by employing sodium acetate as an ion exchanger. The efficiency of the ([Py-2OH]OAc as a promoter for the sono-synthesis of a novel library of condensed products through DABCO-catalyzed Knoevenagel condensation process of adequate active cyclic methylenes and ninhydrin was next investigated using ultimate greener conditions. All of the reactions studied went cleanly and smoothly, and the resulting Knoevenagel condensation compounds were recovered in high yields without detecting the aldol intermediates in the end products. Compared to traditional strategies, the suggested approach has numerous advantages including mild reaction conditions with no by-products, eco-friendly solvent, outstanding performance in many green metrics, and usability in gram-scale synthesis. The reusability of the ionic liquid was also studied, with an overall retrieved yield of around 97% for seven consecutive runs without any substantial reduction in the performance. The novel obtained compounds were further assessed for their in vitro antitumor potential toward three human tumor cell lines: Colo-205 (colon cancer), MCF-7 (breast cancer), and A549 (lung cancer) by employing the MTT assay, and the findings were evaluated with the reference Doxorubicin. The results demonstrated that the majority of the developed products had potent activities at very low doses. Compounds comprising rhodanine (5) or chromane (12) moieties exhibited the most promising cytotoxic effects toward three cell lines, particularly rhodanine carboxylic acid derivative (5c), showing superior cytotoxic effects against the investigated cell lines compared to the reference drug. Furthermore, automated docking simulation studies were also performed to support the results obtained

Mode of gene action and heterosis for physiological, biochemical, and agronomic traits in some diverse rice genotypes under normal and drought conditions

Water scarcity is a crucial environmental stress that constrains rice growth and production. Thus, breeding for developing high-yielding and drought-tolerant rice genotypes is decisive in sustaining rice production and ensuring global food security, particularly under stress conditions. To this end, this study was conducted to evaluate the effects of water deficit on 31 genotypes of rice (seven lines, viz., Puebla, Hispagran, IET1444, WAB1573, Giza177, Sakha101, and Sakha105, and three testers, viz., Sakha106, Sakha107, and Sakha108) and their 21 crosses produced by line × tester mating design under normal and water deficit conditions; this was to estimate the combining ability, heterosis, and gene action for some traits of physiological, biochemical, and yield components. This study was performed during the summer seasons of 2017 and 2018. The results showed that water deficit significantly decreased relative water content, total chlorophyll content, grain yield, and several yield attributes. However, osmolyte (proline) content and antioxidant enzyme activities (CAT and APX) were significantly increased compared with the control condition. Significant mean squares were recorded for the genotypes and their partitions under control and stress conditions, except for total chlorophyll under normal irrigation. Significant differences were also detected among the lines, testers, and line × tester for all the studied traits under both irrigation conditions. The value of the σ²GCA variance was less than the value of the σ²SCA variance for all the studied traits. In addition, the dominance genetic variance (σ2D) was greater than the additive genetic variance (σ2A) in controlling the inheritance of all the studied traits under both irrigation conditions; this reveals that the non-additive gene effects played a significant role in the genetic expression of the studied traits. The two parental genotypes (Puebla and Hispagran) were identified as good combiners for most physiological and biochemical traits, earliness, shortness, grain yield, and 1,000-grains weight traits. Additionally, the cross combinations Puebla × Sakha107, Hispagran × Sakha108, and Giza177 × Sakha107 were the most promising. These results demonstrated the substantial and desirable specific combining ability effects on all the studied traits, which suggested that it could be considered for use in rice hybrid breeding programs

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

4-Thiazolidinones in Heterocyclic Synthesis: Synthesis of Novel Enaminones, Azolopyrimidines and 2-Arylimino-5-arylidene-4-thiazolidinones

The 4-thiazolidinones &lt;strong&gt;3a–d&lt;/strong&gt; were used as a key intermediates for the synthesis of 2-arylimino-5-arylidene-4-thiazolidinones derivatives &lt;strong&gt;7a–p&lt;/strong&gt; &lt;em&gt;via &lt;/em&gt;nucleophilic addition reactions with the arylidene malononitrile. Moreover the 4-thiazolidinones &lt;strong&gt;3a&lt;/strong&gt; and &lt;strong&gt;3c&lt;/strong&gt; condensed with the&lt;strong&gt; &lt;/strong&gt;DMF-DMA to form the corresponding enamines &lt;strong&gt;8&lt;/strong&gt; and &lt;strong&gt;9&lt;/strong&gt; depending on the reaction conditions. Otherwise the 4-thiazolidinone &lt;strong&gt;3b&lt;/strong&gt; reacts regioselectively with DMF-DMA to afford the enaminones &lt;strong&gt;10&lt;/strong&gt; and &lt;strong&gt;11&lt;/strong&gt;, respectively. The latter reacts with many heterocyclic amines affording polyfunctionally substituted fused pyrimidine derivatives &lt;strong&gt;13–18&lt;/strong&gt;. The enamine &lt;strong&gt;8b&lt;/strong&gt; was also reacted with the 3-amino-1,2,4-triazole to afford the acyclic product &lt;strong&gt;19&lt;/strong&gt;, which could not be further cyclized to the corresponding tricyclic system &lt;strong&gt;20&lt;/strong&gt;. Moreover the 4-thiazolidinone &lt;strong&gt;3c&lt;/strong&gt; reacted with the benzenediazonium chloride to afford the arylhydrazones &lt;strong&gt;12&lt;/strong&gt;. The X-ray single crystal technique was employed in this study for structure elucidation and &lt;em&gt;Z/E&lt;/em&gt; potential isomerism configuration determination. The X-ray crystallographic analyses of eight products could be obtained, thus establishing with certainty the structures proposed in this work

Acylation of Heteroaromatic Amines: Facile and Efficient Synthesis of a New Class of 1,2,3-Triazolo[4,5-b]pyridine and Pyrazolo[4,3-b]pyridine Derivatives

1,2,3-Triazolo[4,5-b]pyridines and pyrazolo[4,3-b]pyridines can be readily prepared via cyanoacetylation reactions of 5-amino-1,2,3-triazoles 1a,b and 4-amino- pyrazole 2 followed by subsequent cyclization of the formed cyanoacetamides. Reactions of amines 1a,b with a mixture of p-nitrophenylacetic acid and acetic anhydride under microwave irradiation conditions afforded the corresponding amides 15a,b that underwent cyclization to form 1,2,3-triazolo[4,5-b]pyridines 16a,b upon heating in DMF solutions containing sodium acetate. Reactions of 1a,b with active methylene compounds, including 17a-c, in the presence of zeolites as catalyst also afforded 1,2,3-triazolo[4,5-b]pyridine derivatives 20a-f via the intermediacy of triazole derivatives 19 and not 18