Development of Sustained Release Baricitinib Loaded Lipid-Polymer Hybrid Nanoparticles with Improved Oral Bioavailability

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R² = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.     

A Narrative Review on the Phytochemistry,Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant’s extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.     

Isolation and Characterization of Two Chalcone Derivatives with Anti-Hepatitis B Virus Activity from the Endemic Socotraen Dracaena cinnabari (Dragon’s Blood Tree)

Hepatitis B virus (HBV) infection is prevalent and continues to be a global health concern. In this study, we determined the anti-hepatitis B virus (HBV) potential of the Socotra-endemic medicinal plant Dracaena cinnabari and isolated and characterized the responsible constituents. A bioassay-guided fractionation using different chromatographic techniques of the methanolic extract of D. cinnabari led to the isolation of two chalcone derivatives. Using a variety of spectroscopic techniques, including ¹H-, ¹³C-, and 2D-NMR, these derivatives were identified as 2,4’-dihydroxy-4-methoxydihydrochalcone (compound 1) and 2,4’-dihydroxy-4-methoxyhydrochalcone (compound 2). Both compounds were isolated for the first time from the red resin (dragon’s blood) of D. cinnabari. The compounds were first evaluated for cytotoxicity on HepG2.2.15 cells and 50% cytotoxicity concentration (CC50) values were determined. They were then evaluated for anti-HBV activity against HepG2.2.15 cells by assessing the suppression of HBsAg and HBeAg production in the culture supernatants and their half maximum inhibitory concentration (IC₅₀) and therapeutic index (TI) values were determined. Compounds 1 and 2 indicated inhibition of HBsAg production in a dose- and time-dependent manner with IC₅₀ values of 20.56 and 6.36 μg/mL, respectively.     

Characterization of the Phytochemical Composition and Bioactivities of Anacyclus maroccanus Ball. and Anacyclus radiatus Loisel Aerial Parts: Preliminary Evidence for the Possible Development of Moroccan Plants

In the present study, the phytochemical composition and bioactivities of A. maroccanus (AM) and A. radiatus (AR), two ecotypes collected in the Demnate road and Essaouira regions, respectively, were studied to highlight a pharmacological interest and to enable possible pharmaceutical development. To this end, methanolic and ethyl acetate extracts were prepared for each ecotype by fractionation; next, their phytochemical composition was evaluated by spectrophotometric and chromatographic analysis. Moreover, in line with the available evidence for Anacyclus spp. and their traditional use, a screening of bioactivities, including antioxidant, hypoglycemic, antiglycative, chelating, and antibacterial activities, was performed. The extracts were characterized by high amounts of polyphenols, tannins, and flavonoids, especially in the methanolic extracts; these samples were also enriched in carotenoids despite a lower chlorophyll content. Chlorogenic acid and rutin were the major identified compounds. The extracts also showed interesting hypoglycemic, antiglycative, and antibacterial properties, although with differences in efficacy and potency. Present results provide more scientific basis to the ethnopharmacological uses of Anacyclus spp. and suggest a further interest in AM and AR ecotypes as natural sources of bioactive compounds and/or phytocomplexes for possible pharmaceutical and nutraceutical developments.     

In memory of Professor Ali H. Nayfeh

Nonlinear Dynamics - In this paper, we propose and numerically study a nonlinear, asymmetric, passive metamaterial that achieves giant non-reciprocity with (i) broadband frequency operation and...     

基于图像的二维剪纸自动生成方法

中国剪纸的设计极具挑战性, 要求画面简洁、直观, 还需要表达特定的文化内涵, 且整张剪纸须整体连通。提出了一种基于图像的二维剪纸自动生成方法, 能够将任意数码照片自动转化为剪纸图形。首先,利用图像分割方法建立区域连接图; 接着, 基于该连接图对颜色、边界对比度和区域连通性进行数学建模, 并获得优化目标函数; 最后, 通过模拟退火算法求解目标方程, 自动生成保持图像内容的剪纸图形。还开发了连通性后处理和区域指定等用户交互工具, 允许用户在自动生成的剪纸图形中方便地加入个人设计。实验表明, 所生成的剪纸图形画面简洁、整体连通。 本方法在降低剪纸设计难度的同时还可满足个性化的设计需求, 有助于传播和传承我国的民间剪纸艺术。     

Multiple rogue wave and solitary solutions for the generalized BK equation via Hirota bilinear and SIVP schemes arising in fluid mechanics

The multiple lump solutions method is employed for the purpose of obtaining multiple soliton solutions for the generalized Bogoyavlensky-Konopelchenko(BK) equation. The solutions obtained contain first-order, second-order, and third-order wave solutions. At the critical point,the second-order derivative and Hessian matrix for only one point is investigated, and the lump solution has one maximum value. He's semi-inverse variational principle(SIVP) is also used for the generalized BK equation. Three major cases are studied, based on two different ansatzes using the SIVP. The physical phenomena of the multiple soliton solutions thus obtained are then analyzed and demonstrated in the figures below, using a selection of suitable parameter values.This method should prove extremely useful for further studies of attractive physical phenomena in the fields of heat transfer, fluid dynamics, etc.     

Antimicrobial and Antioxidant Properties of Total Polyphenols of Anchusa italica Retz

Anchusa italica Retz has been used for a long time in phytotherapy. The aim of the present study was to determine the antioxidant and antibacterial activities of extracts from the leaves and roots of Anchusa italica Retz. We first determined the content of phenolic compounds and flavonoids using Folin–Ciocalteu reagents and aluminum chloride (AlCl₃). The antioxidant activity was determined using three methods: reducing power (FRAP), 2.2-diphenyl-1-picrylhydrazyl (DPPH), total antioxidant capacity (TAC). The antimicrobial activity was investigated against four strains of Escherichia coli, two strains of Klebsiella pneumoniae and coagulase-negative Staphylococcus, and one fungal strain of Candida albicans. The results showed that the root extract was rich in polyphenols (43.29 mg GAE/g extract), while the leave extract was rich in flavonoids (28.88 mg QE/g extract). The FRAP assay showed a strong iron reduction capacity for the root extract (IC₅₀ of 0.11 µg/mL) in comparison to ascorbic acid (IC₅₀ of 0.121 µg/mL). The DPPH test determined an IC₅₀ of 0.11 µg/mL for the root extract and an IC₅₀ of 0.14 µg/mL for the leaf extract. These values are low compared to those for ascorbic acid (IC₅₀ of 0.16 µg/mL) and BHT (IC₅₀ 0.20 µg/mL). The TAC values of the leaf and root extracts were 0.51 and 0.98 mg AAE/g extract, respectively. In vitro, the extract showed inhibitory activity against all strains studied, with diameters of zones of inhibition in the range of 11.00–16.00 mm for the root extract and 11.67–14.33 mm for the leaf extract. The minimum inhibitory concentration was recorded for the leaf extract against E. coli (ATB:57), corresponding to 5 mg/mL. Overall, this research indicates that the extracts of Anchusa italica Retz roots and leaves exert significant antioxidant and antibacterial activities, probably because of the high content of flavonoids and polyphenols.     

Antioxidant,Antimicrobial, and Insecticidal Properties of a Chemically Characterized Essential Oil from the Leaves of Dittrichia viscosa L.

Since some synthetic insecticides cause damage to human health, compounds in plants can be viable alternatives to conventional synthetic pesticides. Dittrichia viscosa L. is a perennial Mediterranean plant known to possess biological activities, including insecticidal properties. The chemical composition of an essential oil (EOD) from D. viscosa, as well as its antioxidant, antimicrobial, and insecticidal effects on the cowpea weevil (Callosobruchus maculatus) were determined. Forty-one volatile compounds were identified in EOD, which accounted for 97.5% of its constituents. Bornyl acetate (41%) was a major compound, followed by borneol (9.3%), α-amorphene (6.6%), and caryophyllene oxide (5.7%). EOD exhibited significant antioxidant activity in all tests performed, with an IC₅₀ of 1.30 ± 0.05 mg/mL in the DPPH test and an EC₅₀ equal to 36.0 ± 2.5 mg/mL in the FRAP assay. In the phosphor-molybdenum test, EOD results ranged from 39.81 ± 0.7 to 192.1 ± 0.8 mg AAE/g E. EOD was active on E. coli (9.5 ± 0.5 mm), S. aureus (31.0 ± 1.5 mm), C. albicans (20.4 ± 0.5 mm), and S. cerevisiae (28.0 ± 1.0 mm), with MICs ranging from 0.1 mg/mL to 3.3 mg/mL. We found that 1 µL of EOD caused 97.5 ± 5.0% insect mortality after 96 h in the inhalation test and 60.0 ± 8.3% in the ingestion assay. The median lethal concentration (LC₅₀) was 7.8 ± 0.3 μL EO/L, while the effective concentration in the ingestion test (LC₅₀) was 15.0 ± 2.1 μL EO/L. We found that 20 µL of EOD caused a reduction of more than 91% of C. maculatus laid eggs.