Evaluation of Tadalafil Nanosuspensions and Their PEG Solid Dispersion Matrices for Enhancing Its Dissolution Properties

The aim of this work was to prepare and evaluate Tadalafil nanosuspensions and their PEG 4000 solid dispersion matrices to enhance its dissolution rate. Nanosuspensions were prepared by precipitation/ultrasonication technique at 5°C where different stabilizers were screened for stabilization. Nanosuspensions were characterized in terms of particle size and charge. Screening process limited suitable stabilizers into structurally related surfactants composed of a mixture of Tween80 and Span80 at 1:1 ratio (in percent, weight/volume) in adjusted alkaline pH (named TDTSp-OH). The surfactant mixture aided the production of nanosuspensions with an average particle size of 193 ± 8 nm and with short-term stability sufficient for further processing. Solid dispersion matrices made of dried Tadalafil nanosuspensions or dried Tadalafil raw powder suspensions and PEG 4000 as a carrier were prepared by direct compression. Drying was performed via dry heat or via freeze dry. Drug release studies showed that, in general, tablet formulations made of freeze-dried product exhibited faster initial release rates than the corresponding tablets made of oven-dried products which could be attributed to possible larger crystal growth and larger crushing strengths of oven-dried formulations. At best, 60% of drug was released from solid dispersion matrices, while more than 90% of drug was released from TDTSp-OH nanosuspension within the first 5 min. In conclusion, Tadalafil nanosuspensions obtained using a mixed surfactant system provided rapid dissolution rates of Tadalafil that can theoretically enhance its bioavailability.KEY WORDS: nanosuspension, particle size, solid dispersion, stabilizer, tablets, Tadalafil     

Meloidogyne incognita and Tomato Response to Thiamine,Ascorbic Acid, L-arginine,and L-glutamic Acid

The influence of solutions of ascorbic acid, thiamine, L-arginine, and L-gtutamic acid on egg hatch, juvenile survival, and development and reproduction of Meloidogyne incognita in susceptible and resistant tomatoes was studied. Maximum inhibition of egg hatch occurred at 2,000, 4,000, and 2,000 ppm for ascorbic acid, L-arginine, and L-glutamic acid, respectively. Larval survival was significantly reduced by concentrations of 2,000 ppm ascorbic acid and 1,000 ppm of L-arginine. Maximum inhibition of egg hatch and mortality of juveniles was achieved at a concentration of 4,000 ppm of ascorbic acid and L-arginine. L-glutamic acid and thiamine had respective moderate and minimal toxic effects. Foliar sprays of ascorbic acid, L-arginine, or L-glutamic acid suppressed the numbers of root galls, females, and egg masses on the susceptible tomato cultivar Tropic. Ascorbic acid and L-arginine had highly significant effects when applied to foliage before inoculation with nematodes. Thiamine had little effect. All sprays suppressed the numbers of root galls and females in roots of the resistant cultivar VFN8 when treatments were applied before inoculation. They were not, however, effective as post-inoculation treatments. Growth of a susceptible cultivar was improved by post-inoculation and pre-inoculation treatments when compared with the control plants which had neither nematode infection nor chemical treatment. No positive growth response to chemical treatment was seen in resistant control plants.     

A novel mutation in a large family causes a unique phenotype of Mucolipidosis IV

Mucolipidosis type IV is a rare autosomal recessive lysosomal storage disorder reported among Ashkenazi Jews and to a lesser extent in other ethnic groups. Several mutations have been reported in MCOLN1 which is the only known gene associated with the disorder. Here we report the first Saudi patient with Mucolipidosis type IV from a consanguineous family with two branches having a total of five patients carrying a novel transition mutation, c.1307A > G (p.Y436C) in exon 11. The clinical course of the patient was nonspecific and a lysosomal storage disorder was not highly suspected due to lack of coarse facial features, organomegaly and skeletal findings of dysostosis multiplex. The detailed bioinformatics analysis on the deleterious effects of the mutation is discussed. Emphasis is made on the importance of brain magnetic resonance imaging (MRI) findings and serum gastrin level as key clues to the diagnosis of this often subtle neurodevelopmental disorder.     

BRAF gene: From human cancers to developmental syndromes

The BRAF gene encodes for a serine/threonine protein kinase that participates in the MAPK/ERK signalling pathway and plays a vital role in cancers and developmental syndromes (RASopathies). The current review discusses the clinical significance of the BRAF gene and other members of RAS/RAF cascade in human cancers and RAS/MAPK syndromes, and focuses the molecular basis and clinical genetics of BRAF to better understand its parallel involvement in both tumourigenesis and RAS/MAPK syndromes—Noonan syndrome, cardio-facio-cutaneous syndrome and LEOPARD syndrome.     

An alkalophilic thermostable lipase produced by a new isolate of Bacillus alcalophilus

An extremophilic bacterium, isolated from mangrove detritus, produced an extracellular alkaline-thermostable lipase. The bacterium was identified on the basis of cell morphology, growth characteristics, G+C molar ratio and DNA/DNA hybridization as a strain of Bacillus alcalophilus. The bacterium grew optimally at pH 10.6, 60°C with NaCl tolerance up to 7.5% (w/v). Carbonates and/or bicarbonates enhanced lipase production, while NaCl had an inhibitory effect. Maximum lipase activity was at 60°C at pH 10.6, with approx. 60% of its activity being retained at 80°C after 20min and 80% of its activity was retained at pH 11 after incubation at 60°C. A partially purified lipase had similar stabilities to the crude enzyme.     

Sustained Release Tablets Containing Soluble Polymethacrylates: Comparison with Tableted Polymethacrylate IPEC Polymers

The objective of this study was to compare a novel sustained release tablet formulation that has the potential to be used for drugs of different physicochemical properties using a binary mixture of polymethacrylate polymers in their salt forms with the polymethacrylate interpolyelectrolyte complex (IPEC) tablets in terms of drug release and compactness. Also, we aimed to compare this formulation with an IPEC tablet in terms of drug release. Tablets prepared using Eudragit E-Citrate and Eudragit L-Sodium were more convenient, easier to prepare, and showed better sustained release and compactness characteristics compared to IPEC tablets of similar concentrations and preparation methods.     

Production of biologically active non-woven textiles from recycled polyethylene terephthalate

Recently, various studies have focused on the development of multifunctional non-woven polyethylene terephthalate (PT; polyester) textiles. Herein, we introduce multifunctional non-woven polyester fabrics by pad dry curing silver nitrate (AgNO₃) and aniline monomer into plasma-pretreated non-woven PT textile. This creates a nanocomposite layer of silver nanoparticles (AgNPs) and polyaniline (PANi) on the fabric surface. In order to prepare a non-woven fibrous mat, we applied the melt-spinning technique on previously shredded recycled PT plastic waste. On the surface of the cloth, PANi was synthesized by REDOX polymerization of aniline. Due to the oxidative polymerization, the silver ions (Ag⁺) were converted to Ag⁰NPs. PANi acted as a conductor while AgNPs inhibited the growth of microorganisms. Microwave-assisted curing with trimethoxyhexadecylsilane (TMHDS) gave PT textiles with superhydrophobic properties. The morphological studies were performed using Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EDX). The stiffness and breathability of finished non-woven PT textile materials were analyzed to establish their comfort levels. Both of Escherichia coli and Staphylococcus aureus were used to test the efficacy of the AgNPs-treated textiles as antimicrobial materials. Moreover, the processed polyester textiles showed excellent electrical conductivity and great ultraviolet-ray blocking.     

Essential Oil of Cestrum diurnum L.: GC/MS Analysis,in Vitro and in Silico Anti-HCoV-229E Effects and Inhibitory Activity against LPS-Induced Inflammation

Cestrum diurnum L. (Solanaceae) is a fragrant ornamental tree cultivated in different parts around the world. In this study, the essential oil (EO) of the aerial parts was extracted by hydrodistillation (HD), steam distillation (SD) and microwave-assisted hydro-distillation (MAHD). GC/MS analysis of the three EOs revealed that phytol represents the major component in SD-EO and MAHD-EO (40.84 and 40.04 %, respectively); while in HD-EO it only represented 15.36 %. The SD-EO showed a strong antiviral activity against HCoV-229E with IC₅₀ of 10.93 μg/mL, whereas, MAHD-EO and HD-EO showed a moderate activity with IC₅₀ values of 119.9 and 148.2 μg/mL, respectively. The molecular docking of EO major components: phytol, octadecyl acetate and tricosane showed a strong binding to coronavirus 3-CL (pro). Moreover, the three EOs (50 μg/mL) decreased the levels of NO, IL-6 and TNF-α and suppressed IL-6 and TNF-α gene expression in LPS-induced inflammation model in RAW264.7 macrophage cell lines.