Controlled Release of Aspirin in the Body using Pectin-coated ZIF-8 Nanoparticles.

INTRODUCTION: Zeolitic imidazolate frameworks (ZIFs) play a crucial role among metalorganic frameworks due to their highly desirable properties, including high surface area, appropriate pore size, and excellent thermal and chemical stability. METHOD: In this study, ZIF-8 loaded with aspirin and coated using pectin (ZIF-8/Asp@Pectin) was utilized as a suitable and effective platform for the drug delivery system. The preparation of this coated MOF followed environmentally friendly methods, and aspirin was successfully loaded. RESULT: Characterization of the obtained ZIF-8/Asp@Pectin was performed using X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal gravimetric analysis (TGA), Fourier Transform Infrared (FT-IR) spectroscopy, and BET analysis. CONCLUSION: The release of aspirin from ZIF-8/Asp@Pectin was studied using UV-Vis spectroscopy at 258 nm under in vitro conditions in HCl and PBS buffer solutions.

Supramolecular Cu(ii) nanoparticles supported on a functionalized chitosan containing urea and thiourea bridges as a recoverable nanocatalyst for efficient synthesis of 1H-tetrazoles.

A cost-effective and convenient method for supporting of Cu(ii) nanoparticles on a modified chitosan backbone containing urea and thiourea bridges using thiosemicarbazide (TS), pyromellitic dianhydride (PMDA) and toluene-2,4-diisocyanate (TDI) linkers was designed. The prepared supramolecular (CS-TDI-PMDA-TS-Cu(ii)) nanocomposite was characterized by using Fourier-transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FESEM), thermogravimetry/differential thermogravimetry analysis (TGA/DTA), energy-dispersive X-ray spectroscopy (EDS), EDS elemental mapping and X-ray diffraction (XRD). The obtained supramolecular CS-TDI-PMDA-TS-Cu(ii) nanomaterial was demonstrated to act as a multifunctional nanocatalyst for promoting of multicomponent cascade Knoevenagel condensation/click 1,3-dipolar azide-nitrile cycloaddition reactions very efficiently between aromatic aldehydes, sodium azide and malononitrile under solvent-free conditions and affording the corresponding (E)-2-(1H-tetrazole-5-yl)-3-arylacrylenenitrile derivatives. Low catalyst loading, working under solvent-free conditions and short reaction time as well as easy preparation and recycling, and reuse of the catalyst for five consecutive cycles without considerable decrease in its catalytic efficiency make it a suitable candidate for the catalytic reactions promoted by Cu species.

The role of microRNA-21 (miR-21) in pathogenesis, diagnosis, and prognosis of gastrointestinal cancers: A review.

MicroRNAs (miRNAs) are small non-coding RNAs regulating the expression of several target genes. miRNAs play a significant role in cancer biology, as they can downregulate their corresponding target genes by impeding the translation of mRNA (at the mRNA level) as well as degrading mRNAs by binding to the 3'-untranslated (UTR) regions (at the protein level). miRNAs may be employed as cancer biomarkers. Therefore, miRNAs are widely investigated for early detection of cancers which can lead to improved survival rates and quality of life. This is particularly important in the case of gastrointestinal cancers, where early detection of the disease could substantially impact patients' survival. MicroRNA-21 (miR-21 or miRNA-21) is one of the most frequently researched miRNAs, where it is involved in the pathophysiology of cancer and the downregulation of several tumor suppressor genes. In gastrointestinal cancers, miR-21 regulates phosphatase and tensin homolog (PTEN), programmed cell death 4 (PDCD4), mothers against decapentaplegic homolog 7 (SMAD7), phosphatidylinositol 3-kinase /protein kinase B (PI3K/AKT), matrix metalloproteinases (MMPs), ß-catenin, tropomyosin 1, maspin, and ras homolog gene family member B (RHOB). In this review, we investigate the functions of miR-21 in pathogenesis and its applications as a diagnostic and prognostic cancer biomarker in four different gastrointestinal cancers, including colorectal cancer (CRC), pancreatic cancer (PC), gastric cancer (GC), and esophageal cancer (EC).

The design of multi-responsive nanohydrogel networks of chitosan for controlled drug delivery.

High swelling hydrogel networks (HSHNs) are materials with the ability to high swelling and outstanding candidates for sustained drug delivery systems (DDSs). The present paper demonstrates three different chitosan nanohydrogel networks (CNHN I-III) prepared through covalent and non-covalent interactions. These hydrogels have a high swelling ratio (up to 38-fold their dry weight) in various conditions. Two types of these hydrogels (CNHN I and II), swelled rapidly in an acidic environment, were able to successfully load an extraordinary amount (up to 95 %) of a model drug doxorubicin hydrochloride (DOX.HCl) at a 1:1 ratio (wt./wt.). The CNHN III had substantial swelling in pH 7.4, with a loading capacity of 92 % 5-fluorouracil (5-FU) at a 1:1 ratio (wt./wt.). The CNHN I and II have been considered for systemic drug delivery, while the CNHN III is one of the best candidates for oral drug delivery.

Synthesis of (E)-2-(1H-tetrazole-5-yl)-3-phenylacrylenenitrile derivatives catalyzed by new ZnO nanoparticles embedded in a thermally stable magnetic periodic mesoporous organosilica under green conditions.

ZnO nanoparticles embedded in a magnetic isocyanurate-based periodic mesoporous organosilica (Fe3O4@PMO-ICS-ZnO) were prepared through a modified environmentally-benign procedure for the first time and properly characterized by appropriate spectroscopic and analytical methods or techniques used for mesoporous materials. The new thermally stable Fe3O4@PMO-ICS-ZnO nanomaterial with proper active sites and surface area as well as uniform particle size was investigated for the synthesis of medicinally important tetrazole derivatives through cascade condensation and concerted 1,3-cycloaddition reactions as a representative of the Click Chemistry concept. The desired 5-substituted-1H-tetrazole derivatives were smoothly prepared in high to quantitative yields and good purity in EtOH under reflux conditions. Low catalyst loading, short reaction time and the use of green solvents such as EtOH and water instead of carcinogenic DMF as well as easy separation and recyclability of the catalyst for at least five consecutive runs without significant loss of its activity are notable advantages of this new protocol compared to other recent introduced procedures.

Synthesis and characterization of highly efficient and recoverable Cu@MCM-41-(2-hydroxy-3-propoxypropyl) metformin mesoporous catalyst and its uses in Ullmann type reactions.

The functionalized MCM-41-(2-hydroxy-3-propoxypropyl) metformin was prepared and anchored by copper ions to employ as a catalyst for the Ullmann C-X coupling reaction. The catalyst was characterized by Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy measurements and, N2 adsorption-desorption isotherms. The benefits of this catalyst are the use of inexpensive and non-toxic metformin ligand, easy catalyst/product separation, and catalyst recycling. The catalyst can be reused at least for five repeated cycles without a significant loss of its catalytic activity or metal leaching.

Green synthesis of carbamates and amides via Cu@Sal-Cs catalyzed C-O and C-N oxidative coupling accelerated by microwave irradiation.

A new nano-scale Cu@salicylaldehyde-modified-chitosan (Cu@Sal-CS) was synthesized through a green, eco-friendly and cost-effective technique. The prepared catalyst was characterized using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDXS), and inductively coupled plasma (ICP) analysis. The synthesized Cu@Sal-CS catalyst indicated its performance in the C-O and C-N oxidative coupling using the reaction of 1,3-dicarbonyl derivatives/2- substituted phenols with amides for the preparation of carbamates, as well as in the reaction of aldehydes and various amines in the synthesis of amides. The significant features of this work are operational simplicity of catalyst synthesis, in situ and new modification method, use of an efficient, recoverable, frequently reused and stable catalyst without any loss of catalytic activity, and high yields of the products in short times.

A pH-sensitive nanocarrier based on BSA-stabilized graphene-chitosan nanocomposite for sustained and prolonged release of anticancer agents.

Smart nanomaterials with stimuli-responsive behavior are considered as promising platform for various drug delivery applications. Regarding their specific conditions, such as acidic pH, drug carriers to treatment of tumor microenvironment need some criteria to enhance drug delivery efficiency. In this study, for the first time, pH-sensitive BSA-stabilized graphene (BSG)/chitosan nanocomposites were synthesized through electrostatic interactions between the positively charged chitosan nanoparticles and negatively charged BSG and used for Doxorubicin (DOX) encapsulation as a general anticancer drug. Physicochemical characterization of the nanocomposites with different concentrations of BSG (0.5, 2, and 5wt%) showed effective decoration of chitosan nanoparticles on BSG. Comparing DOX release behavior from the nanocomposites and free BSG-chitosan nanoparticles were evaluated at two pHs of 7.4 and 4.5 in 28 days. It was shown that the presence of BSG significantly reduced the burst release observed in chitosan nanoparticles. The nanocomposite of 2wt% BSG was selected as the optimal nanocomposite with a release of 84% in 28 days and with the most uniform release in 24 h. Furthermore, the fitting of release data with four models including zero-order, first-order, Higuchi, and Korsmeyer-Peppas indicated that the addition of BSG changed the release mechanism of the drug, enabling uniform release for the optimal nanocomposite in first 24 h, compared to that for pure chitosan nanoparticles. This behavior was proved using metabolic activity assay of the SKBR-3 breast cancer cell spheroids exposed to DOX release supernatant at different time intervals. It was also demonstrated that DOX released from the nanocomposite had a significant effect on the suppression of cancer cell proliferation at acidic pH.

A straightforward, environmentally beneficial synthesis of spiro[diindeno[1,2-b:2',1'-e]pyridine-11,3'-indoline]-2',10,12-triones mediated by a nano-ordered reusable catalyst.

A library of new spiro[diindeno[1,2-b:2',1'-e]pyridine-11,3'-indoline]-2',10,12-trione derivatives has been prepared in an efficient, one-pot pseudo four-component method mediated by a reusable heterogeneous nano-ordered mesoporous SO3H functionalized-silica (MCM-41-SO3H) catalyst. Excellent yields, short reaction times, as well as convenient non-chromatographic purification of the products and environmental benefits such as green and metal-free conditions constitute the main advantages of the developed synthetic methodology. The obtained fused indole-indenone dyes would be of interest to pharmaceutical and medicinal chemistry. Furthermore, due to their sensitivity to pH changes, they could be used as novel pH indicators.

Discovery of Cephalosporin-3'-Diazeniumdiolates That Show Dual Antibacterial and Antibiofilm Effects against Pseudomonas aeruginosa Clinical Cystic Fibrosis Isolates and Efficacy in a Murine Respiratory Infection Model.

The formation of biofilms provides a formidable defense for many bacteria against antibiotics and host immune responses. As a consequence, biofilms are thought to be the root cause of most chronic infections, including those occurring on medical indwelling devices, endocarditis, urinary tract infections, diabetic and burn wounds, and bone and joint infections. In cystic fibrosis (CF), chronic Pseudomonas aeruginosa (P. aeruginosa) respiratory infections are the leading cause of morbidity and mortality in adults. Previous studies have shown that many bacteria can undergo a coordinated dispersal event in the presence of low concentrations of nitric oxide (NO), suggesting that NO could be used to initiate biofilm dispersal in chronic infections, enabling clearance of the more vulnerable planktonic cells. In this study, we describe efforts to create "all-in-one" cephalosporin-based NO donor prodrugs (cephalosporin-3'-diazeniumdiolates, C3Ds) that show both direct ß-lactam mediated antibacterial activity and antibiofilm effects. Twelve novel C3Ds were synthesized and screened against a panel of P. aeruginosa CF clinical isolates and other human pathogens. The most active compound, AMINOPIP2 ((Z)-1-(4-(2-aminoethyl)piperidin-1-yl)-2-(((6R,7R)-7-((Z)-2-(2-aminothiazol-4-yl)-2-(((2-carboxypropan-2-yl)oxy)imino)acetamido)-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methoxy)diazene 1-oxide)-ceftazidime 12, showed higher antibacterial potency than its parent cephalosporin and front-line antipseudomonal antibiotic ceftazidime, good stability against ß-lactamases, activity against ceftazidime-resistant P. aeruginosa in vitro biofilms, and efficacy equivalent to ceftazidime in a murine P. aeruginosa respiratory infection model. The results support further evaluation of AMINOPIP2-ceftazidime 12 for P. aeruginosa lung infections in CF and a broader study of "all-in-one" C3Ds for other chronic infections.

Superparamagnetic alginate-based nanocomposite modified by L-arginine: An eco-friendly bifunctional catalysts and an efficient antibacterial agent.

In this protocol, the synthesis, antibacterial activity, and catalytic performance of super paramagnetic iron oxide nanoparticles (SPIONs) coated with L-arginine (Arg) grafted alginate (Alg), as an environmental benign heterogeneous catalyst are reported. The SPIONs coated materials were prepared by the co-precipitation method and characterized by Fourier transform infrared spectrometer (FT-IR), scanning electron microscope (SEM (, transmission electron microscopy (TEM), X-ray diffraction (XRD (, vibrating-sample magnetometer (VSM (, thermal gravimetric analysis (TGA), and energy dispersive X-ray spectroscopy (EDS). Moreover, the synthesized Fe3O4@Alg@CPTMS@Arg was employed for the preparation of 2,4,5-triarylimidazoles derivatives via a one-pot three-component reaction between ammonium acetate, aldehyde derivatives, and benzil under reflux in ethanol. Fe3O4@Alg@CPTMS@Arg exhibited highly effective catalytic activity. Apart from the catalytic activity, a study on the antibacterial activity of the prepared amino acid modified Fe3O4 nanoparticles, Fe3O4@Alg@CPTMS@Arg, was carried out on bacterial strain and compared with the antibacterial activity of the bare alginate. The results shown high antibacterial activity for the prepared nanocomposites against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) compared to alginate. It is assumed that the antibacterial synergism is the combined effect of alginate and L-arginine.

pH-Sensitive magnetite mesoporous silica nanocomposites for controlled drug delivery and hyperthermia.

In clinical applications, chemotherapy and hyperthermia are commonly used together. To achieve this, we synthesized multifunctional magnetite mesoporous silica nanoparticles (MMSNs) coated with a chitosan hydrogel. pH-Responsive chitosan hydrogels (cross-linked glutaraldehyde) were used to cover mesoporous silica pores. The infrared spectroscopy (FT-IR) and electron microscopy images (SEM and TEM) confirm that a hydrogel layer and a silica shell were formed. By applying alternating magnetic fields (AMF) to nanogels, heat generation (43 °C) occurred within a short time. The drug release (tamoxifen) of nanogels was studied for 72 h at different pH and temperatures. Drug release at pH 7.4/T = 37 °C (simulating physiological condition) and pH 5/T = 43 °C (pH simulating endosomes/hyperthermia) were 15 and 70%, respectively, so, drug release was increased with hyperthermia. To determine the biocompatibility of the nanogels, an MTT assay of L929 cells was performed for 24, 48 and 72 h. The results show high biocompatibility of nanogels even at high concentrations (over 80% cell viability after 72 h for all concentrations).

Biocomposites based on hydroxyapatite matrix reinforced with nanostructured monticellite (CaMgSiO4) for biomedical application: Synthesis, characterization, and biological studies.

In this study, a simple and facile strategy was developed for the synthesis of novel hydroxyapatite (HA)/nanostructured monticellite ceramic composites by mechanical method. X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive x-ray spectroscopy (EDS) were used to peruse the phase structure, and morphology of soaked ceramic composites in simulated body fluid (SBF). The in vitro bioactivity of HA-based ceramic composites with nanostructured monticellite ranging from 0 to 50 wt% was evaluated via investigating the formation ability of bone-like calcium phosphates in SBF and the effect of obtained extracts from composites dissolution on osteoblast-like G-292 cell line. Moreover, In vitro cytocompatibility of the HA/monticellite ceramic composites was investigated by MTT, cell growth & adhesion and alkaline phosphatase (ALP) activity assays, and quantitative real-time PCR analysis. The results showed that HA/nanostructured monticellite ceramic composites could induce apatite formation in SBF. The cell proliferation and growth exposed to ceramic composites extracts were significantly stimulated and promoted at a certain concentration range compared to control for various time periods of cell culture. The optimized composite extract enhanced considerably gene expression of G-292 type X collagen (COLX) at different days. Also, G-292 cells were spread and adhered well on the ceramic composite disc. Furthermore, ALP activity of G-292 cells exposed to ceramic composites extracts was dramatically enhanced in comparison with pure HA extract (as control) at different concentrations for various time periods of cell culture. The results suggest that the optimized HA/nanostructured monticellite composite is promising biomaterial for clinical applications such as orthopedic and dentistry.

Stimuli-responsive graphene-incorporated multifunctional chitosan for drug delivery applications: a review.

INTRODUCTION: Recently, the use of chitosan (CS) in the drug delivery has reached an acceptable maturity. Graphene-based drug delivery is also increasing rapidly due to its unique physical, mechanical, chemical, and electrical properties. Therefore, the combination of CS and graphene can provide a promising carrier for the loading and controlled release of therapeutic agents. AREAS COVERED: In this review, we will outline the advantages of this new drug delivery system (DDS) in association with CS and graphene alone and will list the various forms of these carriers, which have been studied in recent years as DDSs. Finally, we will discuss the application of this hybrid composite in other fields. EXPERT OPINION: The introducing the GO amends the mechanical characteristics of CS, which is a major problem in the use of CS-based carriers in drug delivery due to burst release in a CS-based controlled release system through the poor mechanical strength of CS. Many related research on this area are still not fully unstated and occasionally they seem inconsistent in spite of the intent to be complementary. Therefore, a sensitive review may be needed to understand the role of graphene in CS/graphene carriers for future drug delivery applications.

Alginic acid: A mild and renewable bifunctional heterogeneous biopolymeric organocatalyst for efficient and facile synthesis of polyhydroquinolines.

Alginic acid, a widely used naturally occurring carbohydrate which is generally derived from brown seaweeds, can be considered as a bifunctional heterogeneous and green biopolymeric organocatalyst. Alginic acid, without any post-modification with active Bronsted or Lewis acid centers, was found to be a highly active, cost-effective, commercially-available, renewable and recoverable heterogeneous biopolymeric organocatalyst for the expeditious synthesis of polyhydroquinolines (PHQs). Polyhydroquinolines were synthesized from the four-component Hantzsch reaction of ethyl acetoacetate, different aldehydes, ammonium acetate and cyclic 1,3-diones under mild conditions in high to quantitative yields, 75-97%, using alginic acid. Furthermore, alginic acid was found to be reusable for at least 6 consecutive cycles without considerable loss of its catalytic activity.

Chitosan: An efficient biomacromolecule support for synergic catalyzing of Hantzsch esters by CuSO4.

The synergic effect of the chitosan biomacromolecule support for catalyzing of Hantzsch esters formation by CuSO4 has been demonstrated for one-pot and efficient pseudo-four-component reaction to afford a wide range of 1,4-dihydropyridine (DHP) or polyhydroquinoline (PHQ) derivatives. The desired products were simply prepared from different aldehydes, ß-dicarbonyls and ammonium acetate in the presence of a low loading of chitosan supported copper(II) sulfate (CSCS) in EtOH under reflux conditions. The biodegradable CSCS catalyst was characterized by field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy analysis (EDX) methods as well as coupled plasma-atomic emission (ICP-AE) and FT-IR spectroscopy. The CSCS catalyst is recyclable and reused four times without significant loss of its activity.

Sodium alginate: An efficient biopolymeric catalyst for green synthesis of 2-amino-4H-pyran derivatives.

Sodium alginate, a naturally occurring macromolecule, in its granular form and without any post-modification was found to be an efficient and recoverable bifunctional heterogeneous organocatalyst for the domino synthesis of various 2-amino-3-cyano-4H-pyran annulated derivatives through three-component condensation of different aldehydes, malononitrile and diverse 1,3-dicarbonyl compounds under mild conditions. Corresponding 4H-pyran derivatives were obtained in high to excellent yields after 25-150min stirring in 2mL EtOH under reflux conditions in the presence of 10mol% of sodium alginate, equimolar amounts of aldehydes, malononitrile and 1,3-dicarbonyl compounds. The catalyst was easily separated from the reaction mixture to obtain desired products in excellent purity as shown by FTIR and (1)H NMR spectroscopic methods. Avoiding the use of any transition metal, one-pot and multi-component procedure catalyzed by a renewable biopolymer, the reusability of the catalyst, broad substrate scope and operational simplicity are important features of this methodology for preparation of medicinally important compounds.

Cytotoxic and apoptotic effects of synthetic benzochromene derivatives on human cancer cell lines.

With the aim of discovering potential cytotoxic agents, a series of benzochromene derivatives were screened for their cytotoxic activity against seven human cancer cell lines by standard 3-(4, 5-dimethyl thiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis, as the mechanism of cell death, was investigated morphologically by acridine orange/ethidium bromide staining and cell surface expression assay of phosphatidylserine by Annexin V-PE/7-AAD technique. The effects of compounds on reactive oxygen species (ROS) and nitric oxide (NO) generations in three human breast cancer cell lines were also studied. All compounds showed significant cytotoxic activity with inhibitory concentration (IC50) values in the micromolar range (4.6-21.5 µM). The results of apoptosis evaluation suggested that the cytotoxic activity of these compounds in breast cancer cells occurs via apoptosis. MCF-7 cell line showed higher levels of ROS and NO production after treatment with compounds. The increase in ROS production after 4 and 24 h indicated that one of the ways that these compounds can induce apoptosis is by increasing ROS generation. Cytotoxic and apoptotic effects of these compounds in human cancer cells indicated that they can be a good candidate for further pharmacological studies to discover effective anticancer agents.

Electrospun PGA/gelatin nanofibrous scaffolds and their potential application in vascular tissue engineering.

BACKGROUND AND METHODS: In this study, gelatin was blended with polyglycolic acid (PGA) at different ratios (0, 10, 30, and 50 wt%) and electrospun. The morphology and structure of the scaffolds were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. The mechanical properties were also measured by the tensile test. Furthermore, for biocompatibility assessment, human umbilical vein endothelial cells and human umbilical artery smooth muscle cells were cultured on these scaffolds, and cell attachment and viability were evaluated. RESULTS: PGA with 10 wt% gelatin enhanced the endothelial cells whilst PGA with 30 wt% gelatin increased smooth muscle cell adhesion, penetration, and viability compared with the other scaffold blends. Additionally, with the increase in gelatin content, the mechanical properties of the scaffolds were improved due to interaction between PGA and gelatin, as revealed by Fourier transform infrared spectroscopy and differential scanning calorimetry. CONCLUSION: Incorporation of gelatin improves the biological and mechanical properties of PGA, making promising scaffolds for vascular tissue engineering.

An efficient, multicomponent approach for solvent-free synthesis of 2-amino-4H-chromene scaffold.

Solvent-free one-pot synthesis of 2-amino-4H-chromene scaffold is described in a very simple, efficient, and environmentally benign method using sodium carbonate as a cheap and non-toxic catalyst with up to excellent yields.