Physical aging in aqueous nematic gels of a swelling nanoclay: sol (phase) to gel (state) transition.

Aqueous dispersions of geometrically anisometric, nano-sized sodium-montmorillonite (Na-Mt) display a sol-gel transition at very low solids concentrations. The microstructure of the gel formed at very low ionic strengths is considered electrostatically repulsive with a nematic character, and the gel state at ionic strengths where Debye length is of the order of particle size is conjectured to be free of physical aging. We investigated the nature of osmotically prepared Na-Mt dispersions at low ionic strength (∼10-5 M), below and above the gel point. The sol phase exhibited very low yield stress compared to the gel state, without any sign of physical aging, thus behaving as an equilibrium state. In contrast, the gel exhibited signatures of physical aging, that is, an evolving microstructure that consolidated with time when left undisturbed thus behaving as out of equilibrium state. The physical aging behaviour became more pronounced at Na-Mt concentrations far above the gel point. A critical shear rate existed, below which no stable flows were possible in the gel state representing the microstructural reorganization timescale. Overall, Na-Mt dispersions in the gel state behave like systems that were out of equilibrium with an ever-evolving microstructure, in opposition to the assumption that low ionic strength Na-Mt gels are in an equilibrium phase. The possible origin of physical aging, such as the reversible orientation of Brownian anisotropic particles, stiffening of an existing microstructure, or reorganization of microstructure towards minimal energy configuration is discussed in detail.

In Vivo Antistress Effects of Synthetic Flavonoids in Mice: Behavioral and Biochemical Approach.

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones (F1-F6) and flavonols (OF1-OF6), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC50 of 31.46 ± 1.46 µg/mL and 25.54 ± 1.21 µg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC50 values of 174.24 ± 2.71 µg/mL and 122.33 ± 1.98 µg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.

Effects of Artemisia macrocephala Jacquem on Memory Deficits and Brain Oxidative Stress in Streptozotocin-Induced Diabetic Mice.

Different species of Artemisia have been reported to have therapeutic potential in treating various health disorders, including diabetes and memory dysfunction. The present study was planned to evaluate the effects of Artemisia macrocephala Jacquem crude extract and its subfractions as antiamnesic agents in streptozotocin-induced (STZ) diabetic mice. The in vivo behavioral studies were performed using the Y Maze test and novel object recognition test (NORT) test at doses of 100 and 200 mg/kg of crude extract and 75 and 150 mg/kg of fractions. The in vitro and ex vivo anticholinesterase activities, along with biochemical parameters (superoxide dismutase, catalase, glutathione and lipid peroxidation) in the brain, were evaluated. Blood glucose levels were monitored with a glucometer; crude extract and fractions reduced the glucose level considerably, with some differences in the extent of their efficacies. The crude extract and fractions demonstrated significant inhibitory activity against cholinesterases (AChE and BuChE) in vitro. Crude, chloroform and ethyl acetate extract were found to be more potent than the other fractions, with IC50 of Crd-Am = 116.36 ± 1.48 and 240.52 ± 1.35 µg/mL, Chl-Am = 52.68 ± 1.09 and 57.45 ± 1.39 µg/mL and Et-Am = 75.19 ± 1.02 and 116.58 ± 1.09 µg/mL, respectively. Oxidative stress biomarkers like superoxide dismutase, catalase and glutathione levels were elevated, whereas MDA levels were reduced by crude extract and all fractions with little difference in their respective values. The Y-maze test and novel object recognition test demonstrated declines in memory impairment in groups (n = 6) treated with crude extract and fractions as compared to STZ diabetic (amnesic) group. The most active fraction, Chl-Am, was also subjected to isolation of bioactive compounds; three compounds were obtained in pure state and designated as AB-I, AB-II and AB-III. Overall, the results of the study showed that Artemisia macrocephala Jacquem enhanced the memory impairment associated with diabetes, elevated acetylcholine levels and ameliorated oxidative stress. Further studies are needed to explore the beneficial role of the secondary metabolites isolated in the present study as memory enhancers. Toxicological aspects of the extracts are also important and need to be evaluated in other animal models.

Magnetic resonance imaging of endometriosis: a common but often hidden, missed, and misdiagnosed entity.

Endometriosis is a common benign and chronic inflammatory gynaecological disease due to functional endometrial glands and stroma in an ectopic location outside the uterine cavity. It affects 5-10% of reproductive age group women in the peak age of 24-29 years. However, women with infertility and chronic pelvic pain have an even greater prevalence, accounting for 30-50% and 90% of cases, respectively. Although it is a common entity, patients often get a delayed diagnosis because it is often subtle (hidden), missed, or confused with mimics, leading to misdiagnosis, which significantly affects patients' quality of life because they live in constant pain from undiagnosed endometriosis. Laparoscopy followed by histopathological confirmation is the gold standard for diagnosis, but it is an invasive procedure. MRI is an excellent non-invasive modality that helps in non-invasive diagnosis, with excellent delineation of the disease extent, and thus provides a presurgical mapping of the disease, which is helpful for the operating surgeon. Radiologists should be aware of all possible spectrum and diagnose this early and provide a detailed structured report mapping the entire extent of the disease process, which helps in effective treatment planning and successful outcomes in improving patients' quality of life.

Mineral carbonation for serpentine mitigation in nickel processing: a step towards industrial carbon capture and storage.

A proof-of-concept for the carbonation-assisted processing of ultramafic nickel ores is presented. Carbonation converts serpentine, the primary gangue or undesirable mineral, to magnesite. It prevents slime coating of fine gangue minerals on pentlandite, the main nickel-bearing mineral, during froth flotation, and improves nickel recovery and concentrate grade. Additionally, CO2 is captured and stored in the form of solid carbonates, thus removing it from the atmosphere. Microflotation experiments demonstrated improved nickel recovery (61.2 to 87.4 wt%) and concentrate grade (20.6 to 24.7 wt%) in carbonated vs. uncarbonated systems. The mechanism behind the improved nickel flotation was investigated by zeta potential measurements, optical imaging microscopy, X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry. These analyses confirmed the absence of slime coating in the carbonated system under the flotation conditions tested. Finally, a preliminary techno-economic analysis was performed to evaluate the cost metrics of incorporating carbonation into nickel mineral processing.

Rheological implications of pH induced particle-particle association in aqueous suspension of an anisotropic charged clay.

Kaolinite particles are geometrically anisometric and electrostatically anisotropic. Until recently, the charge of both basal faces of kaolinite was assumed to be independent of pH, and the isoelectric point (IEP) of the edge surface was thought to occur at pH 4-6. Therefore, kaolinite suspensions were expected to have an edge-face association at low pH. However, recent atomic force microscopy (AFM) studies have shown that the kaolinite alumina basal face and edge surface carry a pH-dependent surface charge with an IEP at pH 5-6 and ∼ 3, respectively. Here, we revisit the modes of particle association in kaolinite suspensions and apply Derjaguin-Landau-Verwey-Overbeek (DLVO) theory to study the rheological implications of surface charges of various kaolinite faces from recent AFM-based studies. Specifically, aging within the linear viscoelastic region, small amplitude oscillatory shear behavior (strain amplitude and frequency response), and critical stress behavior were studied as a function of pH. Kaolinite suspensions (40 wt%) exhibited two-step structure recovery after shear rejuvenation and two-step yielding at pH less than the IEP of the alumina basal face. In addition, the storage modulus (G') and critical stress required to stabilize the flow followed non-monotonic behavior as a function of pH. At low pH, the silica face-alumina face mode of association was expected to be dominant rather than the edge-face microstructure. A peak in the G'vs. pH curve at pH 4.5-5 was correlated with the silica face-alumina face attraction estimated from DLVO theory, which passes through a maximum at approximately the same pH. Based on these observations, we propose a qualitative state diagram for kaolinite suspensions in the pH-concentration space.

GC/MS analysis, anti-leishmanial and relaxant activity of essential oil of Chenopodium ambrosioides (L.) from Malakand region.

Chenopodium ambrosioides is abundantly available in Malakand region. As constituents and concentrations of essential oils vary based on its geographical location, we carried our current study to extract and evaluate its possible relaxant activity in rabbits' jejunum and anti-leishmanial activity against promastigotes of Leishmania tropica. The essential oil was obtained from aerial fresh parts through steam distillation followed by GC/MS analysis. Antispasmodic activity was performed on spontaneous and KCl induced contractions. Curves for calcium concentration response (CCRCs) were prepared with and without different concentrations of essential oils and verapamil - a standard calcium channel blocker as per our reported procedures. GC/MS analysis indicated that the essential oil contains 4-carene (56.59%) and o-cymene (41.46%), the two most abundant compounds previously reported from this species. The LD50 value for acute toxicity is 279.66±2.2mg/kg. The essential oil have significant antileishmanial activity with LC50 of Log10 (1.83±0.0026) ×10-6mg/ml, potent relaxant activity on rabbits' jejunal preparations with respective EC50 = 1.46±0.15mg/ml for spontaneous activity. For KCl (80mM) induced contractions, EC50=0.26±0.02mg/ml. In CCRCs, the oil produced a right shift as exhibited by verapamil. More, its relaxant activity, which is mediated through calcium channel blocking mechanism, proves a rationale for its traditional use in gut spasm.

Does male factor infertility impact on self-esteem and sexual relationship?

Nonsomatic factors play a significant role in erectile dysfunction. We assessed the impact on men suffering from male factor infertility by employing the validated Self-Esteem and Relationship questionnaire (SEAR) and compared the scores with controls. Men with primary infertility were asked to fill SEAR questionnaire. Normal fertile men visiting clinic for unrelated problem or normal male accompanying infertile patients constitute the control group. Transformed score of each domain and total score of SEAR questionnaire and means were compared. Data were analysed by R version 5.2. Univariate and multivariate analyses were done to determine factors predicting self-esteem and total relationship score. There were 45 men each in the study and control groups. The mean transformed self-esteem score and total score of infertile men were significantly lower as compared to controls (74.44 versus 95.83) and (73.54 versus 95.86) p-value of <.0001. Longer duration of infertility, advanced age, diabetes and higher education were factors significantly lowering the scores on univariate analysis, and on multivariate analysis, diabetes was the only significant predictor of total SEAR score in infertile men. Infertility leads to lower self-esteem, sexual performance and confidence among infertile men as compared to controls. The relationship score worsens with increasing duration of infertility.

Urdu translation and validation of premature ejaculation diagnostic tool (PEDT).

OBJECTIVE: To validate an Urdu translation of premature ejaculation diagnostic tool (PEDT) by analyzing the association of this diagnostic tool with the clinical diagnosis of premature ejaculation (PE) and intravaginal ejaculatory latency time (IELT). METHODS: This cross-sectional study was conducted at the urology section of the Aga Khan University Hospital, Karachi, for six months duration, from July 2018 to December 2018. In our study 108 subjects, aged 20 to 50 years, who were in a stable sexual relationship (heterosexual) for a minimum duration of six months, were asked to fill the Urdu version of PEDT, 61 with PE and 47 without PE. RESULTS: The two groups matched for mean age, duration of relationship and education level. The duration of 1.2 (±0.5) minutes was the mean self-estimated IELT in the PE group and 3.7±0.9 minutes in patients without PE. There was a significant negative correlation of 0.6 (p-value <0.001) between the PEDT score and self-estimated IELT. The test-retest reliability for each item was found to be significant for each individual item (≥ 0.84, p-value <0.001) and 0.94 was the correlation coefficients of the total score, showing an excellent test-retest reliability. 0.93 was the Cronbach's alpha score (95% Confidence interval = 0.905 - 0.948) indicating a significant internal consistency in the Urdu version of PEDT. CONCLUSIONS: The Urdu version of PEDT is a valid tool to define and quantify PE objectively, with adequate internal consistency. This version of PEDT has a good negative correlation with self-estimated IELT and excellent correlation with clinical PE.

Relaxant activity of different fractions of fruits of Rosa moschata J.

The current work is an attempt to know that in which fraction(s) the relaxant constituents of Rosa moschata concentrate. Crude methanolic extract of Rosa moschata was prepared as per our reported procedure. Sub fractions of methanol extract were extracted with different solvents in increasing order of polarity i.e. n-hexane > chloroform > ethyl acetate > n-butanol > residual aqueous fractions. Different concentrations (0.01, 0.03, 0.1, 0.3, 1, 3, 5 and 10 mg/ml) of the fractions were tested on spontaneous contractions and KCl induced contractions on rabbits' jejunal preparations. Calcium Concentration Response Curves (CCRCs) in the presence and absence of the test fractions using verapamil were constructed to understand its mechanisms. EtOA fraction was more relaxant with EC50 values 0.812±0.149 mg/ml on spontaneous and 2.01±0.08 mg/ml on KCl induced contractions. we also found right shift in its EC50 values expressed as log [Ca++]M values. In presence of 0.3 mg/ml EtOA fraction, its EC50 value was -2.22±0.035 vs control EC50 -2.71±0.21. For n-BuOH fraction, EC50 value was -1.82±0.00 vs control with EC50 -2.28±0.049 at concentration of 0.3 mg/ml. Ethyl acetate fraction of Rosa moschata was more potent and is therefore can be a target for activity guided isolation of calcium channel antagonists.

Synthesis, crystal studies and biological evaluation of flavone derivatives.

Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. These compounds were characterized by NMR spectroscopy and single crystal X-ray Diffraction. Compound F1 and F3 were re-crystallized from their concentrated solutions in chloroform ethyl acetate mixture while F2 was re-crystallized in ethyl acetate n-hexane mixture. Compound F1 and F3 are monoclinic (space group P21/c) with lattice parameters: [a, b, c (A) / ß (°)] = 13.332 (2), 15.616 (2) / 6.2898 (8) and 13.9716 (15), 7.1868 (7), 13.6912 (14) / 91.113(6) respectively. Compound F2 is Triclinic (space group P-1) and has lattice parameters: [a, b, c (Å) / α, ß, γ (°)] = 6.5002 (6), 8.3801 (9), 13.5989 (14) / 89.348(5), 85.141(4), 84.521(5). Antioxidant, antibacterial and cytotoxic profile was investigated. The compounds showed moderate to less activity on 1,1-diphenyl-2-picryl-hydrazyl (DPPH), Hydrogen peroxide (H/2/O/2) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) models of radical scavenging activity while promising antibacterial potentials were recorded. Furthermore, these molecules can also be used as potential candidates for new antitumor agents.

A possible mechanistic approach of synthetic flavonoids in the management of pain.

Flavonoids are phenolic compounds that have always attracted pharmaceutical researchers and food manufacturers. Nature has indirectly provided us flavones in our daily diet i.e. tea, fruits, juices and vegetables. Flavones have got special position in research field of natural and synthetic organic chemistry due to their biological capabilities. Three substituted flavone derivatives have been synthesized from substituted O-hydroxy acetophenones and 4-trifluoromethyl benzaldehyde in good yield. The structures have been established by different spectroscopic techniques like 1HNMR 13CNMR, IR spectroscopy. The compounds were then screened for their enzyme inhibition potential and antinociceptive response in mice models with writhings induced by acetic acid, tail immersion and formalin-induced nociception assay procedures and structure activity relationship was established. The effects following pretreatment with naloxone were also studied to reveal the involvement of opioid receptors in the antinociceptive action. The flavone derivatives showed moderate to weak inhibition against LOX. Moreover, significant to moderate decrease in the number of abdominal constrictions, increase in paw-licking response time in both phases and a significant raise in latency time in nociception models. Moreover, the antinociceptive response was significantly attenuated by pretreatment with opioid receptor antagonist suggesting the involvement of opioidergic system in the analgesic action. The flavone derivatives showed analgesic response in all models of nociception suggesting the possible involvement of opioidergic system in the antinociceptive action.

Synthetic flavonols and flavones: A future perspective as anticancer agents.

A series of flavonoid derivatives, flavones (F1-F3) and flavonols (OF1-OF3) were synthesized. Their structures were confirmed through various spectroscopic techniques and elemental analysis. These were then tested for cytotoxic activity against mouse fibroblast (NIH 3T3), human endothelial cervical (HeLa) and breast (MCF7) cell lines in vitro by MTT assay. The flavonol series showed prominent potentials than the flavones. The compound OF2 in flavonols exhibited greater potentials MCF7 cell with IC50 value of 0.96µM and OF3 has 1.04µM. In contrast, the OF3 exhibited higher activity against HeLa cell with IC50 value of 0.51µM and OF2 has 1.06µM. The compounds OF2 and OF3 exhibited activity against mouse fibroblast (NIH 3T3) cell with IC50 values 2.48 and 1.24µM. The OF1 was found to be moderate to inactive against all cells. Cytotoxic screening of the tested flavones, F1 to F3 were also active against all cells but the activity was less in comparison to flavonol series of compounds suggestion the possible involvement of hydroxyl (OH) at position 3 in case of flavonols. These results indicated a cheering scaffold that may lead to innovation of potent anti-breast cancer activity.

Nootropic effects of synthetic flavonoid derivatives on scopolamine induced memory impairment in mice via cholinesterase inhibition and antioxidant system.

The synthesized flavonoid derivatives (flavonols and flavones) were subjected for in-vitro anticholinesterase evaluation followed by assessment of in-vivo memory enhancing effects using animal models. The ex-vivo analysis of brain was carried out and portions were subjected foe estimation of biochemical parameters that includes AChE, ACh, SOD and CAT level. Among tested flavonoids, the para substituted chloro containing flavonol (OF2) and flavone (F2) revealed a considerable in-vitro AChE and BuChE % inhibition with an IC50 values. It was observed from the in-vivo results that OF1-OF3 at 12.5 mg/kg b.w has significance over F1-F3 in ameliorating the memory in scopolamine induced amnesic mice in passive avoidance step through and novel object recognitions test. Scopolamine elevated significantly the AChE level, decreased the contents of ACh, SOD and CAT in the brain in amnesic model. The flavonoid derivatives showed significant effects on these changes by decreasing the ex-vivo AChE contents, enhancing the level of ACh, SOD and CAT suggesting their possible role as cholinesterase and antioxidant. These findings suggest that synthetic flavonols and flavones may serve as potential candidates for developing safer and effective nootropic agents.

Antidiabetic potential of flavonoids from Artemisia macrocephalla Jaquem in streptozotocin-induced diabetic rats: Pharmacological and biochemical approach.

Plants belongs to Asteraceae family are reported to be rich in major phytochemical including flavonoids and are documented to acquire antidiabetic response. Antidiabetic effects of salvigenin, eupatilin and cirsilineol were screened on in-vitro enzyme inhibition and in-vivo streptozotocin animal models. Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) produced antidiabteic responses in streptozotocin model for diabetes. All natural flavonoids reduces the blood glucose level to a significant level (*P<0.05, **P<0.01, ***P<0.001, n=8) but promising results were observed in eupatilin at dose of 7.5mk/kg (364.12±4.3 to 128.41±4.2mg/dL, n=8) and at dose of 7.5mk/kg 363.65±4.8 to 126.14±5.1mg/dL, n=8). Administration of salvigenin, eupatilin and cirsilineol (7.5 and 15mg/kg) for 28 days showed a substantial fall (*P<0.05, **P<0.01, ***P<0.001, n=8) in total cholesterol, LDL and triglcerides (TGs) in comparison to diabetic model. The isolated flavonoids reduced considerably the serum ALP, SGPT and SGOT in rats intoxicated with streptozotocin. The results indicate that the flavonoids may be useful in the development of new antidiabetic drugs.

Isolation of flavonoides from Artemisia macrocephala anticholinesterase activity: Isolation, characterization and its in vitro anticholinesterse activity supported by molecular docking.

In this study the flavonoids isolated from Artemisia macrocephala were screened out for anticholinesterase activity. The isolated flvanoids were characterized by HNMR, NOESY, COSY, HMBC, HSQC and mass spectroscopy. The compounds (1-4) in appropriate quantities were isolated from chloroform fraction using gravity column chromatography by eluting ethyl acetate/n-hexane solvent system. The flavonoids were characterized and resulted in the form of mono substituted methoxy flavones to tri substituted flavones. Ellman's assay techniques were used to find out enzyme inhibition. Operating environment (MOE) software was used for molecular docking studies. Compounds (1), (2) and (3) showed 88.42±2.76, 84.50±1.60 and 90.16±2.98 percent inhibition of the acetyl cholinesterase (AChE) respectively at 1000µg/mL concentrations with IC50 value 165, 60, 65µg/mL respectively which were comparable to that of standard galanthamine. While for butyryl cholinesterase (BChE), (1), (2) and (3) showed 91.63±4.32, 81.03±3.53 and 87.69±2.84 percent inhibitions respectively at 1mg/mL as compared to the standard galanthamine which caused 96.50±2.41 percent inhibition at the same concentration. Whereas, compound (4) exhibited moderate activity for both the enzymes. Molecular docking studies confirmed the experimental AChE and BChE inhibitory activities of the test samples by their virtue of multiple teractions with target enzymes. The results confirm that the specie has biologically active constituents that are more useful for the management of several neurodegenerative ailments like ataxia, Parkinson's disease, Alzeimer's disease and some other types of dementia.

Sesquiterpene lactone! a promising antioxidant, anticancer and moderate antinociceptive agent from Artemisia macrocephala jacquem.

BACKGROUND: Sesquiterpene lactones (STLs) make a diverse and huge group of bio-active constituents that have been isolated from several plant families. However, the greatest numbers are present in Asteraceae family having more than 3000 different reported structures. Recently several researchers have reported that STLs have significant antioxidant and anticancer potentials. METHODS: To investigate the antioxidant, anticancer and antinociceptive potentials of STLs, gravity column chromatography technique was used for isolation from the biologically rich chloroform fraction of Artemisia macrocephala Jacquem. The antioxidant activity of the isolated STLs was determined by DPPH and ABTS free radical scavenging activity, anticancer activity was determined on 3 T3, HeLa and MCF-7 cells by MTT assay while the antinociceptive activity was determined through acetic acid induced writhings, tail immersion method and formalin induced nociception method. RESULTS: The results showed that the STLs of Artemisia macrocephala possesses promising antioxidant activity and also it decreased the viability of 3 T3, HeLa and MCF-7 cells and mild to moderate antinociceptive activity. CONCLUSION: Sesquiterpenes lactones (STLs) are widely present in numerous genera of the family Asteraceae (compositae). They are described as the active constituents used in traditional medicine for the treatment of various diseases. The present study reveals the significant potentials of STL and may be used as an alternative for the management of cancer. Anyhow, the isolated compound is having no prominent antinociceptive potentials.

Creatinine-based non-phospholipid vesicular carrier for improved oral bioavailability of Azithromycin.

CONTEXT: Novel, safe, efficient and cost effective nano-carriers from renewable resources have got greater interest for enhancing solubility and bioavailability of hydrophobic dugs. OBJECTIVES: This study reports the synthesis of a novel biocompatible non-phospholipid human metabolite "Creatinine" based niosomal delivery system for Azithromycin improved oral bioavailability. METHODS: Synthesized surfactant was characterized through spectroscopic and spectrometric techniques and then the potential for niosomal vesicle formation was evaluated using Azithromycin as model drug. Drug loaded vesicles were characterized for size, polydispersity index (PDI), shape, drug encapsulation efficiency (EE), in vitro release and drug-excipient interaction using zetasizer, atomic force microscope (AFM), LC-MS/MS and FTIR. The biocompatibility of surfactant was investigated through cells cytotoxicity, blood hemolysis and acute toxicity. Azithromycin encapsulated in niosomes was investigated for in vivo bioavailability in rabbits. RESULTS: The vesicles were spherical with 247 ± 4.67 nm diameter hosting 73.29 ± 3.51% of the drug. Surfactant was nontoxic against cell cultures and caused 5.80 ± 0.51% hemolysis at 1000 µg/mL. It was also found safe in mice up to 2.5 g/kg body weight. Synthesized surfactant based niosomal vesicles revealed enhanced oral bioavailability of Azithromycin in rabbits. CONCLUSIONS: The results of the present study confirm that the novel surfactant is highly biocompatible and the niosomal vesicles can be efficiently used for improving the oral bioavailability of poor water soluble drugs.

Synthesis, characterization and antinociceptive activities of Novel 2-(2,4-dichlorophenyl)-4H-chromen-4-one.

A novel flavone derivative has been synthesized in good yield from ketone and aldehyde. The structure has been established by different spectroscopic techniques like 1H NMR, 13C NMR, IR and elemental analysis. The compound was then screened for its acute toxicity and antinociceptive activity studies on animal model. The novel compound was safe upto a maximum dose of 500mg/kg body weight oral dose in mice and showed 65.92 and 82.18% pheriperal analgesic activity at 15 and 30mg/kg body weight doses. Central antinociceptive activity of the compound was 53.13 and 64.44% at 15 and 30mg/kg body weight respectively.

Synthesis, characterization, antioxidant and brine shrimp cytotoxic activity of novel 3-benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea.

In the present research work novel ephedrine based thiourea derivative, 3-benzothioyl-1-(3-hydroxy-3-phenyl -3-propyl)-1-methylthiourea 4is synthesized and then characterized elemental analyzed via various techniques i.e., Proton NMR, carbon13 NMR and fatherly confirmed via X-ray crystallography. Compound 4 was then screened for their possible antioxidant and cytotoxic potentials. Benzoyl chloride was treated with an equimolar potassium thiocyanate in acetone to achieve benzoyl isothiocyantes. It was then treated with an equimolar (1R, 2S)-(-)-Ephedrine to obtain the 3-benzothioyl-1-(3-hydroxy-3-phenyl-3-propyl)-1-methyl thiourea4. It was then screened for antioxidant and cytotoxic potentials. The compound 4 showed excellent antioxidant activity almost comparable to ascorbic acid (standard) and have significant cytotoxic activity with LC50 value 05±0.58 ppm.