Background Apremilast (APM) is a novel, orally administered small molecule drug approved for treatment of psoriasis or psoriatic arthritis. Due to its low solubility and permeability, it is classified as a class IV drug according to BCS classification. Dose titration is recommended during APM treatment due to its tolerability and twice-daily dosing regimen issues. Materials and Methods In this study, three different APM-loaded PLGA nanoparticles (F1–F3) were prepared by single emulsion and evaporation method. Based on particle size, PDI, zeta potential (ZP), entrapment efficiency (%EE), drug loading (%DL), and spectral characterization, the nanoparticles (F3) were optimized. The F3 nanoparticles were further evaluated for in vitro release and in vivo pharmacokinetic studies in rats. Results The optimized nanoparticles (F3) had particles size 307.3±8.5 nm with a low PDI value 0.317, ZP of −43.4±2.6 mV, EE of 61.1±1.9% and DL of 1.9±0.1%. The in vitro release profile showed a sustained release pattern of F3 nanoparticles of APM. The pharmacokinetic results showed 2.25 times increase in bio-availability of F3 nanoparticles compared to normal APM suspension. Moreover, significant increase in half-life and mean residence time confirms long-term retention of F3 nanoparticles. Conclusion Bioavailability enhancement along-with long-term retention of the APM-loaded PLGA nanoparticles might be helpful for the once-daily regimen treatment.

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This work was conducted to study the chemical composition, antioxidant, antibacterial, and antifungal activities of essential oil and hydrolat from Withania frutescens. The essential oil was extracted by hydrodistillation. The chemical characterization was performed using gas chromatography-mass spectrometry (GC/MS). The antioxidant activity was studied using four different assays (DPPH, TAC, FRAP, and β-carotene bleaching). The antibacterial activity test was carried out on multidrug-resistant bacteria including Gram-negative and Gram-positive strains. Antifungal activity was tested on Candida albicans and Saccharomyces cerevisiae. The yield of essential oil (EO) obtained by hydrodistillation of W. frutescens was 0.31% majorly composed of camphor, α-thujone, carvacrol, and thymol. Regarding the antioxidant activities, the concentration of the sample required to inhibit 50% of radicals (IC50) of EO and hydrolat were 14.031 ± 0.012 and 232.081 ± 3.047 µg/mL (DPPH), 4.618 ± 0.045 and 8.997 ± 0.147 µg/mL (FRAP), 0.091 ± 0.007 and 0.131 ± 0.004 mg AAE/mg (TAC), 74.141 ± 1.040% and 40.850 ± 0.083% (β-carotene), respectively. Concerning the antibacterial activity of essential oil and hydrolat, the minimum inhibitory concentration (MIC) values found were 0.006 ± 0.001 and 6.125 ± 0.541 µg/mL (Escherichia coli 57), 0.003 ± 0.001 and 6.125 ± 0.068 µg/mL (Klebsiella pneumoniae), 0.001 ± 0.0 and 6.125 ± 0.046 µg/mL (Pseudomonas aeruginosa) and 0.012 ± 0.003 and 6.125 ± 0.571 µg/mL (Staphylococcus aureus), respectively. MIC values of essential oil and hydrolat vs. both C. albicans and S. cerevisiae were lower than 1/20,480 µg/mL. Based on the findings obtained, essential oils of Withania frutescens can be used as promising natural agents to fight free radical damage and nosocomial antibiotic-resistant microbes.

The incidence of diabetes is increasing worldwide. Chronic neuropathic pain occurs in approximately 25% of diabetic patients. Tramadol, an atypical analgesic with a unique dual mechanism of action, is used in the management of painful diabetic neuropathy. It acts on monoamine transporters to inhibit the reuptake of norepinephrine (NE), serotonin (5-HT), and dopamine (DA). The purpose of this study was to evaluate the effects of diabetes on the brain neurotransmitter alterations induced by tramadol in rats, and to study the hepatic and renal toxicities of the drug. Eighty Sprague-Dawley rats were divided randomly into two sets: the normal set and the diabetic set. Diabetes was induced in rats. Tramadol was administered orally once daily for 28 days. The levels of DA, NE, and 5-HT in cerebral cortex, thalamus/hypothalamus, midbrain, and brainstem were evaluated in rats. In addition, the renal toxicity and histopathological effects of the drug were assessed. The induction of diabetes altered neurotransmitter levels. Oral administration of tramadol significantly decreased the neurotransmitter levels. Diabetes significantly altered the effects of tramadol in all brain regions. Tramadol affected function and histology of the liver and kidney. The clinical effects of tramadol in diabetic patients should be stressed.

A literature survey revealed no suitable “reversed phase-high performance thin layer chromatography (RP-HPTLC)” method for the analysis of rivaroxaban in nanoparticle (NP) formulations.

Caralluma europaea (Guss.) N.E.Br.: (C. europaea) is a wild medicinal plant belonging to the family Apocynaceae. It is commonly used in traditional medicines for treating several diseases. The present work aims to evaluate the anti-inflammatory, antibacterial, and antifungal potentials of C. europaea fractions including hydro ethanol (ET CE), n-butanol (But CE), and polyphenol (Poly CE). The chemical composition of hydroethanol, n-butanol, and polyphenol-rich fractions from C. europaea were determined using GC-MS after silylation. The anti-inflammatory effect of hydroethanol, n-butanol, and polyphenol-rich fractions was studied by carrageenan-induced paw edema. Antibacterial and antifungal activities of hydroethanol, n-butanol, and polyphenol-rich fractions against Gram-positive bacteria, Gram-negative bacteria, and yeasts were assessed using the disc diffusion and micro-dilution assays. The findings of the chemical characterization affirmed the presence of interesting bioactive compounds in C. europaea fractions. The polyphenol-rich fraction was the best inhibitor of edema by75.68% after 6 h of treatment. The hydroethanol fraction was the most active against both bacteria and yeasts. This study contributes to society as it provides potential bioactive compounds in C. europaea extract, which may help in fighting nosocomial antibiotic-resistant microbes.

In this work, two varieties of Anacyclus pyrethrum (L.) including Anacyclus pyrethrum var. pyrethrum (L.) and Anacyclus pyrethrum var. depressus (Ball) Maire were evaluated for their mineral and chemical compositions, total phenolic and flavonoid contents, and antimicrobial and antioxidant activities using hydroalcoholic extracts from their different parts (leaves, capitula, roots, and seeds). The phytochemical and mineral compositions were carried out using standard methods. The antioxidant activity was determined using the DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2-azino-bis 3-ethylbenzothiazolin-6-sulfonic acid), and FRAP (ferric reducing antioxidant power) tests. The antimicrobial activity was assayed using the agar diffusion, minimum inhibitory concentration, and minimum bactericidal concentration methods. The results of the chemical analysis showed that both varieties contained interesting mineral and chemical compositions with potentially active compounds; among them, N-isobutyl-2,4-heptadiene-6-monoynamide and cinnamic acid were detected in the Anacyclus pyrethrum var. pyrethrum (L.) only while thiadiazolo [5,4-d] pyrimidin-7-amine and N-isobutyl-2,4-undecadiene-8,10-diynamide compounds were limited to the Anacyclus pyrethrum var. depressus (Ball) Maire. In vitro antioxidant and antimicrobial activities of the two varieties demonstrated that the different parts had prominent antioxidant and antimicrobial properties. The principal component analysis (PCA) showed great similarity in the activity of the leaves, capitula, and seeds of both plants and a high difference in roots. Anacyclus pyrethrum var. pyrethrum roots were characterized by a high content in phenols and flavonoids and better antibacterial activities compared to Anacyclus pyrethrum var. depressus (Ball) Maire roots, which were characterized by better antioxidant activities. From this study, it can be concluded that the two varieties of Anacyclus pyrethrum (L.) showed promising mineral and chemical compositions with antioxidant and antimicrobial properties.

As part of our search for new compounds having antiviral effects, the prepared 2-aminonaphthalimide series was examined for its activity against the herpes simplex viruses HSV-1 and HSV-2. This represents the first study of the antiviral effects of this class of compounds. The new series of 2-amino-1H-benzo [de]isoquinoline-1,3-diones was examined against HSV-1 and HSV-2 using a cytopathic effect inhibition assay. In terms of effective concentration (EC50), furaldehyde, thiophene aldehyde and allyl isothiocyanide derivatives 14-16 showed potent activity against HSV-1 (EC50 = 19.6, 16.2 and 17.8 μg/mL), compared to acyclovir as a reference drug (EC50 = 1.8 μg/mL). Moreover, 14 and 15 were found to exhibit valuable activity against HSV-2. Many of the tested compounds demonstrated weak to moderate EC50 values relative to their inactive parent compound (2-amino-1H-benzo [de]isoquinoline-1,3-dione), while compounds 7, 9, 13, 14, 15, 16, 21 and 22 were the most active set of antiviral compounds throughout this study. The cytotoxicity (CC50), EC50, and the selectivity index (SI) values were determined. In a OPEN ACCESSMolecules 2015, 20 5100 molecular docking study, the ligand-receptor interactions of compounds 1-24 and their parent with the HSV-1 thymidine kinase active site were investigated using the Molegro Virtual Docker (MVD) software. Based on the potent anti-HSV properties of the previous naphthalimide condensate products, further exploration of this series of 2-amino-1H-benzo [de]isoquinoline-1,3-diones is warranted.