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Objectives: Diclofenac exhibits limited solubility, low bioabsorption and gastric toxicity. The objective of the study was to address the above limitations and to design a multi-particulate formulation for the chronotherapy of RA. Materials and Methods: Solid dispersions of DC with SSG and GG were prepared. Uniform-sized (∼400 μm) non-pareil seeds were coated with solid dispersions to produce immediate-release pellets (DMP-1 and DMP-2) and controlled-release pellets (DMP-3 and DMP-4). The resultant controlled-release pellets were further layered with methacrylate polymers to obtain pulsatile-release pellets (DMPP). Solubility, FTIR, DSC, micrometrics, SEM, drug content, drug release, pharmacokinetics, and stability studies were performed for DMPP. Results: The solubility of DC was improved by 164-folds due to the presence of hydrophilic carriers in the solid dispersions. No chemical and physical interactions were noticed in FTIR spectra and also in thermograms. A fluidized bed processor facilitated the production of high-quality, circular, and regular pellets with an angle of repose less than 19.5 degrees and DC content between 95.18% and 98.87%. The maximum drug was released from DMPP at the end of 12 hours. DMP-1 and DMP-2 pellets had 2 hr of drug release and pulsatile, controlled-release pellets had a 6 hr lag phase followed by 12 hr controlled release. Both DMP-1 and DMP-2–immediate showed first-order release followed by Hixson-Crowell kinetics, whereas DMPP pellets followed zero-order release with Higuchi’s kinetics. The maximum concentration of DC in plasma was 400.8 ng/mL at 5 hr for DMP-2 and 381.1 ng/mL at 14 hr for DMPP-5. The solubility of DC was increased with the application of solid dispersion and in turn increased the pharmacokinetics. The pellets were plausibly stable over a period of 90 days. Conclusion: Thus, multi-particulate pulsatile systems of DC were as effective as chronotherapeutics in the treatment of circadian rhythm-based ailments such as RA.

Objectives: Isolation of enzymes and experiments on them require great effort and cost and are time-consuming. Therefore, it is important to extend the usability of the enzymes by immobilizing them. In this study our purpose was to immobilize the enzyme aldose reductase (AR) and to optimize the experimental conditions of the immobilized AR and compare them to those of free AR. Materials and Methods: AR was isolated from bovine liver and the enzyme immobilized in photographic gelatin by cross-linking with glutaraldehyde. Then the optimum conditions for free and immobilized AR in terms of pH, temperature, and storage were characterized by determining the enzyme activity. Results: Following immobilization, the optimum pH and temperature levels for free AR, which were pH 7.0 and 60°C, slightly altered to pH 7.5 and 50°C. The enzyme activity of the immobilized AR was maintained at about 65% after reusing 15 times. Moreover, immobilized AR maintained 95% of its original activity after 20 days of storage at 4°C, while the retained activity of the free AR was 85% of the original. Conclusion: Our experiments indicated that the conditions that affect enzyme activity might alter following immobilization. Once the optimum experimental conditions are fixed, the immobilized AR can be stored and reused with efficiency higher than that of free AR. Moreover, this study provides an insight into the advantages of using immobilized AR in enzyme assays rather than free AR.

Objectives: Early detection of bone cancer is critical for treating symptoms, minimizing pain, and increasing overall quality of life. It is critical to develop novel radiopharmaceuticals with high labeling efficiency and stability for the diagnosis of bone cancer. The goal of this research is to design a novel radiopharmaceutical that may be utilized to diagnose bone cancer. Materials & Methods: In this study, ibandronate sodium (IBD), a bisphosphonate analogue, was radiolabeled with technetium-99m (99mTc) and quality control tests of the newly developed radiopharmaceutical ([99mTc]Tc-IBD) were done using radioactive thin layer chromatography (RTLC). After that, the incorporation of [99mTc]Tc-IBD into hydroxyapatite crystals and a human bone osteosarcoma cell line (U2OS) was tested. Results: According to the results obtained, optimal radiolabeling procedure was obtained for [99mTc]Tc-IBD with 200 μg.mL-1 IBD, 20 μg stannous chloride and 99mTc with 37 MBq radioactivity. The reaction mixture was adjusted to pH 5.5 and incubated at room temperature for 15 min. The radiochemical purity of [99mTc]Tc-IBD was found to be greater than 95% at room temperature for up to 6 h. In addition, chromatography analysis showed >95% [99mTc]Tc-IBD complex formation with promising stability for up to 24 h in saline and up to 2 h in cell medium. The percent binding of IBD to hydroxyapatite was 83.70±3.67 and the logP of [99mTc]Tc-IBD was -1.1014. The radiolabeled complex showed a higher rate of cell incorporation to U2OS cells compared to Reduced/Hydrolyzed 99mTcO4-. Conclusion: The newly produced radiopharmaceutical is very promising, according to the results of in vitro cell culture, hydroxyapatite binding, and quality studies, and will be a step forward for further studies in nuclear medicine for bone cancer diagnostics.

CQD are small carbon nanoparticles smallerl than 10 nm comprising distinctive properties, which have become an obligatory tool for traceable targeted delivery, biomedical research, and different therapy applications. The objective of the present work was to consolidate the current literature on the synthesis, characterization techniques, and biomedical applications of CQD. Two types of synthetic methods viz. top-down approach and bottom-up approach were used for the synthesis of CQD. The top-down approach includes the arc-discharge method, laser ablation method, and electrochemical method. The bottom-up approach includes the thermal method, microwave-assisted method, hydrothermal and aqueous method, and the template method. In this review, we explain the recent progress of CQD in the biomedical field, focusing on their synthetic methods and characterization, followed by different applications. Carbon dots have extensive adequacy for and bioimaging and drug delivery studies. Although more cytotoxicity studies of carbon dots are needed, the data above suggest a bright future for carbon dots in drug delivery and bioimaging studies.

The aim of the present study was to formulate levocetirizine hydrochloride (LCD)-loaded chitosan nanoparticles at submicron level with high entrapment efficiency and prolonged effect for optimizing the plasma drug concentration enhancing bioavailability. LCD was successfully incorporated into chitosan nanoparticles by spray drying for the purpose of oral application. characteristics were evaluated in detail. LCD was successfully loaded into the polymeric matrices by spray drying. Characterization of the nanoparticles including encapsulation efficiency, particle size, zeta potential, morphology, polydispersity index, solid-state characterizations, and LCD quantification by high performance liquid chromatography was performed. The release pattern of LCD from the nanoparticles was determined using a dialysis tube in simulated intestinal fluid (pH 6.8). release profiles indicated prolonged release of LCD from the nanoparticles that followed the Korsmeyer-Peppas kinetic model. Chitosan-based LCD-loaded polymeric nanoparticles appear to be a promising drug delivery system for the active agent.

Hydrogels are macromolecular networks able to absorb and release water/biological fluids in a reverse-phase manner, in response to specific environmental stimuli. Such stimuli-sensitive behavior makes hydrogels interesting for the design of smart devices applicable to a variety of technological fields. They are able to absorb and retain 10-20% and up to 1000 times the water or biological fluids than their dry weight can. The aim of this study was to extend the work on drug delivery in the stomach at pH 2-2.2. The authors synthesized sodium alginate (SA)/poly(vinyl alcohol) (PVA) hydrogels. These hydrogels were characterized by fourier transform infrared spectroscopy and scanning electron microscopy, and the swelling properties of the hydrogels were examined at different pH values, in different salts, at different temperatures, and in different acids and bases. The authors studied and reported the swelling effects or variations such as the effects of salts, acids, bases, temperature, and pH. The results for the crosslinking agent glutaraldehyde showed that 8 mL of glutaraldehyde had a higher swelling rate compared to that of 10 mL and 12 mL. In this work the authors studied the swelling degree in different acids and bases. It is concluded that the degree of swelling decreases with increases in the concentration of glutaraldehyde and also depending on the concentrations of the acids. The swelling degrees of PVA/SA hydrogels gradually increase with increases in the concentrations of acids (low pH). The swelling of hydrogels decreases with increases in pH (>7) or at high alkaline. Based on the results for salt solutions the swelling behavior was found to be in the order: K >Na >Ca >Mg .

Objectives: Aim of the current study was to evaluate the stress-protective effect of oligopeptides-homologues of the adrenocorticotropic hormone (ACTH) fragment 15-18 on morphogenetic signs of stress reaction of the adrenal glands under acute cold exposure (CE) in rats. Materials and Methods: The acute cold stress was reproduced by placing random-bred male rats in a freezer at a temperature of -18°C for 2 hours. The peptides-homologous of ACTH15-18 acetyl-(D-Lys)-Lys-Arg-Arg-amide (KK-1) and acetyl-(D-Lys)-Lys-(D-Arg)-Arg-amide (KK-5) and the reference medicine (Sema) were administered intranasally in a dose of 20 mg/kg 30 minutes before and after CE. Rectal temperature was measured before and 10 min after CE. Zona glomeruloza, zona fasciculata, zona reticularis, and the area of cells and nuclei of adrenocorticocytes of the zona fasciculata were measured. Results: KK-1 significantly prevented structural changes in the adrenal cortex and medulla and stabilized the secretory activity of glucocorticoidproducing cells. However, the congestion of the capillaries of the zona fasciculata and zona reticularis remained in some locations. Zona fasciculata cells had a marked tendency to decrease, and the area of nuclei significantly decreased (p<0.05) recovering the width to control animals’ markers. KK-5 had a more marked recovery of the adrenal glands (a greater saturation of cytoplasm of adrenocorticocytes of zona glomerulosa and zona fasciculata). The number of chromaffin cells at rest was increased in the adrenal medulla. KK-5 statistically significantly normalized both the area of cells (p<0.05) and the area of nuclei (p<0.05) of the zona fasciculata, unlike KK-1, which reliably restored only the marker of the nuclei area. Some morphometric parameters of acute stress hypertrophy remained in the adrenal glands of rats receiving Sema. Conclusion: KK-1 and KK-5 prevented the manifestation of acute stress reactions in the adrenal cortex of rats. KK-5 had a more marked stressprotective effect compared with the peptide KK-1. Both study substances exceeded the reference medicine Sema. KK-5 is a promising stressprotector and frigoprotector.

Tobacco smoke from regular cigarettes contains a number of harmful chemicals such as nicotine, arsenic, benzene, carbon monoxide, heavy metals, and tobacco-derived nitrosamines. About 1% of over 7000 chemical substances formed by burning tobacco are identified as the leading causes or possible risk factors of smoking-related diseases such as lung cancer, cardiovascular diseases, and emphysema. The concept of heating tobacco without combustion and smoke has been designed for more than two decades. The products developed with this idea, known as \"Heat-Not-Burn\" tobacco cigarettes, were first introduced in the late 1980s but did not achieve commercial success. However, the tobacco giants have been trying to remarket tobacco heating systems with new technological and modified features for over 10 years. I-Quit-Ordinary-Smoking (iQOS ) is one of the latest heat-not-burn tobacco products, first launched in Japan and Italy. The company then made a submission to the Food and Drug Administration as a modified-risk tobacco product application to sell its own tobacco-heating device iQOS under its Marlboro brand in the USA with reduced-risk claims in 2016, but it was rejected. This device is, however, now sold in more than four dozen countries. There are some striking claims that iQOS , which is described as a novel hybrid product between traditional cigarettes and electronic cigarettes, offers an alternative way to substantially reduce the amount of harmful components compared with traditional cigarettes by its new technology in which tobacco is heated up to 350°C instead of being burnt. It is claimed to produce vapour containing nearly 90% less toxic substances than cigarette smoke and not be a source of second-hand smoking negatively affecting indoor air quality. The purpose of this article is to objectively review the potential effects of iQOS on human health and the environment by searching and integrating the published research findings.

The aim was the synthesis of novel substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones and screening for their hypoglycemic activity and anti-inflammatory activity, as well as molecular docking studies to find out active potential lead molecules. Substituted aromatic aldehydes, thiazolidine-2,4-dione, and morpholine on Mannich reaction gave the title compounds. They were characterized by physical and spectral methods. hypoglycemic activity was examined in alloxan induced Wistar albino rats by tail tipping method. anti-inflammatory activity was tested by human red blood cell (HRBC) membrane stabilization and protein denaturation. Using AutoDock, molecular docking studies were carried out to find out the best fit ligands. Series of substituted 5-[morpholino(phenyl)methyl]-thiazolidine-2,4-diones were synthesized and chemically they were confirmed by spectral techniques. Acute toxic studies of hypoglycemic activity results revealed that compounds 4c, 4h, and 4n exhibited good activity at 35 mg/kg body weight. Chronic toxic study results indicated that compounds 4h and 4n exhibited good activity at 70 mg/kg body weight. Anti-inflammatory activity results indicated the highest inhibition was shown by compounds 4k and 4f at 500 μg/mL in HRBC membrane stabilization. In protein denaturation, the highest inhibition was shown by compound 4k at 500 μg/mL. In molecular docking studies, compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX-1 and COX-2 actives sites. Microwave irradiation produced high yield in short reaction times. The presence of electron releasing groups at the para position of the phenyl ring may give the ability to produce hypoglycemic activity and the presence of electron withdrawing groups at the para position of the phenyl ring causes anti-inflammatory activity. The results showed that some compounds exhibited good hypoglycemic and anti-inflammatory activities. Compounds 4h and 4n exhibited higher binding affinity at PPARγ receptor protein and compound 4k exhibited higher binding affinity at COX isoenzymes' active sites in molecular docking studies.

In the present study, the antioxidant potency of ethyl acetate (AcOEt) and methanol (MeOH) extracts from the aerial parts of L. species was investigated for the first time. species L. such as Woronow ex Schischk., Besser, Boiss. & Heldr., subsp. Pall. ex Sm., Parolly & Nordt, (L.) W.Koch, M.Bieb., (M.Bieb.) Koso-Pol., Freyn & Sint., and L. growing in Turkey were collected and evaluated for their antioxidant capacity by using 1.1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and lipid peroxidation (LPO) inhibition methods. The highest activities as a scavenger of DPPH radicals were found in the AcOEt extracts of (M.Bieb.) Koso-Pol (IC =0.49 mg/mL), and (IC =0.75 mg/mL); α-tocopherol was used as a positive control. On the other hand, in the LPO assay, the highest activities were determined in AcOEt and MeOH extracts (at 5 mg/mL) of and (84-94%). This report gives important information about the antioxidant capacity of L. species. This research on antioxidant capacity proves that the use of some species used in Eastern Anatolia (in salads) is correct. With this screening study performed in L. species growing in Turkey, in the future, it is planned to isolate antioxidant compounds from the most active strains of L.