Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.
Chitosan, a prestigious versatile biopolymer, has recently received considerable attention as a promising biosorbent for recovering gold ions, mainly Au(III), from aqueous solutions, particularly in modified forms. Confirming the assertion, this paper provides an up-to-date overview of Au(III) recovery from aqueous solutions by raw (unmodified) and modified chitosan. A particular emphasis is placed on the raw chitosan and its synthesis from chitin, characteristics of raw chitosan and their effects on metal sorption, modifications of raw chitosan for Au(III) sorption, and characterization of raw chitosan before and after modifications for Au(III) sorption. Comparisons of the sorption (conditions, percentage, capacity, selectivity, isotherms, thermodynamics, kinetics, and mechanisms), desorption (agents and percentage), and reusable properties between raw and modified chitosan in Au(III) recovery from aqueous solutions are also outlined and discussed. The major challenges and future prospects towards the large-scale applications of modified chitosan in Au(III) recovery from aqueous solutions are also addressed.
Various concentrations of Mg into fixed amount of cellulose nanocrystals (CNC)-doped ZnO were synthesized using facile chemical precipitation. The aim of present study is to remove dye degradation of methylene blue (MB) and bactericidal behavior with synthesized product. Phase constitution, functional group analysis, optical behavior, elemental composition, morphology and microstructure were examined using XRD, FTIR, UV-Vis spectrophotometer, EDS and HR-TEM. Highly efficient photocatalytic performance was observed in basic medium (98%) relative to neutral (65%), and acidic (83%) was observed upon Mg and CNC co-doping. Significant bactericidal activity of doped ZnO nanoparticles depicted inhibition zones for G -ve and +ve bacteria ranging (2.20 - 4.25 mm) and (5.80-7.25 mm) for E. coli and (1.05 - 2.75 mm) and (2.80 - 4.75 mm) for S. aureus at low and high doses, respectively. Overall, doped nanostructures showed significant (P
The current study describes synthesis of diindolylmethane (DIM) derivatives based-thiadiazole as a new class of urease inhibitors. Diindolylmethane is natural product alkaloid reported to use in medicinal chemistry extensively. Diindolylmethane-based-thiadiazole analogs (1-18) were synthesized and characterized by various spectroscopic techniques 1HNMR, 13C-NMR, EI-MS and evaluated for urease (jack bean urease) inhibitory potential. All compounds showed excellent to moderate inhibitory potential having IC50 value within the range of 0.50 ± 0.01 to 33.20 ± 1.20 µM compared with the standard thiourea (21.60 ± 0.70 µM). Compound 8 (IC50 = 0.50 ± 0.01 µM) was the most potent inhibitor amongst all derivatives. Structure-activity relationships have been established for all compounds. The key binding interactions of most active compounds with enzyme were confirmed through molecular docking studies.
Faecal sterols detection is a promising method for identifying sources of faecal pollution. In this study, faecal contamination in water samples from point source (sewage treatment plants, chicken farms, quail farms and horse stables) was extracted using the solid phase extraction (SPE) technique. Faecal sterols (coprostanol, cholesterol, stigmasterol, beta-sitosterol and stigmastanol) were selected as parameters to differentiate the source of faecal pollution. The results indicated that coprostanol, cholesterol and beta-sitosterol were the most significant parameters that can be used as source tracers for faecal contamination. Chemometric techniques, such as cluster analysis, principal component analysis and discriminant analysis were applied to the data set on faecal contamination in water from various pollution sources in order to validate the faecal sterols' profiles. Cluster analysis generated three clusters: coprostanol was in cluster 1, cholesterol and beta-sitosterol formed cluster 2, while cluster 3 contained stigmasterol and stigmastanol. Discriminant analysis suggested that coprostanol, cholesterol and beta-sitosterol were the most significant parameters to discriminate between the faecal pollution source. The use of chemometric techniques provides useful and promising indicators in tracing the source of faecal contamination.
This study aimed to develop a novel electrospun polyacrylonitrile (PAN) nanofiber membrane with the enhanced antibacterial property. The PAN nanofiber membrane was first subjected to alkaline hydrolysis treatment, and the treated membrane was subsequently grafted with chitosan (CS) to obtain a CS-modified nanofiber membrane (P-COOH-CS). The modified membrane was then coupled with different dye molecules to form P-COOH-CS-Dye membranes. Lastly, poly(hexamethylene biguanide) hydrochloride (PHMB) was immobilized on the modified membrane to produce P-COOH-CS-Dye-PHMB. Physical characterization studies were conducted on all the synthesized nanofiber membranes. The antibacterial efficacies of nanofiber membranes prepared under different synthesis conditions were evaluated systematically. Under the optimum synthesis conditions, P-COOH-CS-Dye-PHMB was highly effective in disinfecting a high concentration of Escherichia coli, with an antibacterial efficacy of approximately 100%. Additionally, the P-COOH-CS-Dye-PHMB exhibited an outstanding wash durability as its antibacterial efficacy was only reduced in the range of 5%-7% even after 5 repeated cycles of treatment. Overall, the experimental results of this study suggested that the P-COOH-CS-Dye-PHMB is a promising antibacterial nanofiber membrane that can be adopted in the food, pharmaceutical, and textile industries.
Detail chemical investigations on the stem bark of Mesua daphnifolia gave three triterpenoids and four xanthones. They are friedelin (1), friedelan-1,3-dione (2), lup-20(29)- en-3ss-ol (3), cudraxanthone G (4), ananixanthone (5), 1,3,5-trihydroxy-4-methoxyxanthone (6) and euxanthone (7). These chemical constituents were tested in vitro for their cytotoxic activities against four cell lines, MDA-MB-231 (human estrogen receptor negative breast cancer), HeLa (cervical carcinoma), CEM-SS (T-lymphoblastic leukemia) and CaOV3 (human ovarian cancer). Compound 4 showed a broad spectrum of activity against the MDA-MB-231, HeLa and CEM-SS cell lines with IC5 0 values of 1.3, 4.0 and 6.7 microg/ml respectively. Meanwhile, the other compounds 1, 2, 3, 5, 6 and 7 gave only selective activities against the cell lines.
Previously reported amphiphilic diblock copolymer with pendant dendron moieties (P71D3) has been further evaluated in tumor-bearing mice as a potential drug carrier. This P71D3-based micelle of an average diameter of 100nm was found to be biocompatible, non-toxic and physically stable in colloidal system up to 15days. It enhanced the in vitro potency of doxorubicin (DOX) in 4T1 breast tumor cells by increasing its uptake, by 3-fold, compared to free DOX. In 4T1 tumor-bearing mice, the tumor growth rate of P71D3/DOX (2mg/kg DOX equivalent) treated group was significantly delayed and their tumor volume was significantly reduced by 1.5-fold compared to those treated with free DOX. The biodistribution studies indicated that P71D3/DOX enhanced accumulation of DOX in tumor by 5- and 2-fold higher than free DOX treated mice at 15min and 1h post-administration, respectively. These results suggest that P71D3 micelle is a promising nanocarrier for chemotherapeutic agents.
Matched MeSH terms: Anthracenes/chemistry; Doxorubicin/chemistry*; Drug Carriers/chemistry; Polymers/chemistry*; Nanoparticles/chemistry
Oral delivery of pharmaceuticals requires that they retain their physical and chemical attributes during transit within the gastrointestinal (GI) tract, for the manifestation of desired therapeutic profiles. Solid lipid nanoparticles (SLNs) are used as carriers to improve the absorption of hydrophobic drugs. In this study, we examine the stability of amphotericin B (AmB) and paracetamol (PAR) SLNs in simulated GI fluids during gastric emptying. On contact with the simulated fluids, the particles increased in size due to ingress of the dissolution media into the particles. Simulated gastric emptying revealed that the formulations had mean sizes <350nm and neutral surface charges, both of which are optimal for intestinal absorption of SLNs. There was ingress of the fluids into the SLNs, followed by diffusion of the dissolved drug, whose rate depended on the solubility of the loaded-drug in the particular medium. Time-of-flight secondary ion mass spectrometry analyses indicated that drug loading followed the core-shell model and that the AmB SLNs have a more drug-enriched core than the PAR SLNs do. The AmB SLNs are therefore a very suitable carrier of AmB for oral delivery. The stability of the SLNs in the simulated GI media indicates their suitability for oral delivery.
Matched MeSH terms: Acetaminophen/chemistry; Amphotericin B/chemistry; Drug Carriers/chemistry*; Lipids/chemistry*; Nanoparticles/chemistry*
Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert virucidal effects, but the binding site on the capsid was unknown. In this study, the ligand interacting site of silymarin was determined in silico and validated in vitro. Moreover, the potential of EV-A71 to develop resistance against silymarin was further evaluated. Molecular docking of silymarin with the capsid of EV-A71 indicated that silymarin binds to viral protein 1 (VP1) of EV-A71, specifically at the GH loop of VP1. The in vitro binding of silymarin with VP1 of EV-A71 was validated using recombinant VP1 through ELISA competitive binding assay. Continuous passaging of EV-A71 in the presence of silymarin resulted in the emergence of a mutant carrying a substitution of isoleucine by threonine (I97T) at position 97 of the BC loop of EV-A71. The mutation was speculated to overcome the inhibitory effects of silymarin. This study provides functional insights into the underlying mechanism of EV-A71 inhibition by silymarin, but warrants further in vivo evaluation before being developed as a potential therapeutic agent.
Silver nanoparticles (AgNPs) are among the most widely synthesized and used nanoparticles (NPs). AgNPs have been traditionally synthesized from plant extracts, cobwebs, microorganisms, etc. However, their synthesis from wing extracts of common insect; Mang mao which is abundantly available in most of the Asian countries has not been explored yet. We report the synthesis of AgNPs from M. mao wings extract and its antioxidant and antimicrobial activity. The synthesized AgNPs were spherical, 40-60 nm in size and revealed strong absorption plasmon band around at 430 nm. Highly crystalline nature of these particles as determined by Energy-dispersive X-ray analysis and X-ray diffraction further confirmed the presence of AgNPs. Hydrodynamic size and zeta potential of AgNPs were observed to be 43.9 nm and -7.12 mV, respectively. Fourier-transform infrared spectroscopy analysis revealed the presence of characteristic amide proteins and aromatic functional groups. Thin-layer chromatography (TLC) and Gas chromatography-mass spectroscopy (GC-MS) analysis revealed the presence of fatty acids in the wings extract that may be responsible for biosynthesis and stabilization of AgNPs. Further, SDS-PAGE of the insect wing extract protein showed the molecular weight of 49 kDa. M. mao silver nanoparticles (MMAgNPs) exhibit strong antioxidant, broad-range antibacterial and antifungal activities, (66.8 to 87.0%), broad-range antibacterial and antifungal activities was found with maximum zone of inhibition against Staphylococcus aureus MTCC 96 (35±0.4 mm) and Fusarium oxysporum f. sp. ricini (86.6±0.4) which signifies their biomedical and agricultural potential.
Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.
Surface acoustic wave mediated transductions have been widely used in the sensors and actuators applications. In this study, a shear horizontal surface acoustic wave (SHSAW) was used for the detection of food pathogenic Escherichia coli O157:H7 (E.coli O157:H7), a dangerous strain among 225 E. coli unique serotypes. A few cells of this bacterium are able to cause young children to be most vulnerable to serious complications. Presence of higher than 1cfu E.coli O157:H7 in 25g of food has been considered as a dangerous level. The SHSAW biosensor was fabricated on 64° YX LiNbO3 substrate. Its sensitivity was enhanced by depositing 130.5nm thin layer of SiO2 nanostructures with particle size lesser than 70nm. The nanostructures act both as a waveguide as well as a physical surface modification of the sensor prior to biomolecular immobilization. A specific DNA sequence from E. coli O157:H7 having 22 mers as an amine-terminated probe ssDNA was immobilized on the thin film sensing area through chemical functionalization [(CHO-(CH2)3-CHO) and APTES; NH2-(CH2)3-Si(OC2H5)3]. The high-performance of sensor was shown with the specific oligonucleotide target and attained the sensitivity of 0.6439nM/0.1kHz and detection limit was down to 1.8femto-molar (1.8×10(-15)M). Further evidence was provided by specificity analysis using single mismatched and complementary oligonucleotide sequences.
3-Thiazolylcoumarin derivatives 1-14 were synthesized via one-pot two step reactions, and screened for in vitro α-glucosidase inhibitory activity. All compounds showed inhibitory activity in the range of IC50 = 0.12 ± 0.01-16.20 ± 0.23 μM as compared to standard acarbose (IC50 = 38.25 ± 0.12 μM), and also found to be nontoxic. Molecular docking study was carried out in order to establish the structure-activity relationship (SAR) which demonstrated that electron rich centers at one and electron withdrawing centers at the other end of the molecules showed strong inhibitory activity. All the synthesized compounds were characterized by spectroscopic techniques such as EI-MS, HREI-MS, (1)H NMR and (13)C NMR. CHN analysis was also performed.
Being an emerging transdermal delivery tool, nanoemulgel, has proved to show surprising upshots for the lipophilic drugs over other formulations. This lipophilic nature of majority of the newer drugs developed in this modern era resulting in poor oral bioavailability, erratic absorption, and pharmacokinetic variations. Therefore, this novel transdermal delivery system has been proved to be advantageous over other oral and topical drug delivery to avoid such disturbances. These nanoemulgels are basically oil-in-water nanoemulsions gelled with the use of some gelling agent in it. This gel phase in the formulation is nongreasy, which favors user compliance and stabilizes the formulation through reduction in surface as well as interfacial tension. Simultaneously, it can be targeted more specifically to the site of action and can avoid first-pass metabolism and relieve the user from gastric/systemic incompatibilities. This brief review is focused on nanoemulgel as a better topical drug delivery system including its components screening, formulation method, and recent pharmacokinetic and pharmacodynamic advancement in research studies carried out by the scientists all over the world. Therefore, at the end of this survey it could be inferred that nanoemulgel can be a better and effective drug delivery tool for the topical system.
Photocatalytic fuel cell (PFC) is a potential wastewater treatment technology that can generate electricity from the conversion of chemical energy of organic pollutants. An immobilized ZnO/Zn fabricated by sonication and heat attachment method was applied as the photoanode and Pt/C plate was used as the cathode of the PFC in this study. Factors that affect the decolorization efficiency and electricity generation of the PFC such as different initial dye concentrations and pH were investigated. Results revealed that the degradation of Reactive Green 19 (RG19) was enhanced in a closed circuit PFC compared with that of a opened circuit PFC. Almost 100% decolorization could be achieved in 8 h when 250 mL of 30 mg L(-1) of RG19 was treated in a PFC without any supporting electrolyte. The highest short circuit current of 0.0427 mA cm(-2) and maximum power density of 0.0102 mW cm(-2) was obtained by PFC using 30 mg L(-1) of RG19. The correlation between dye degradation, conductivity and voltage output were also investigated and discussed.
Nanoparticles have been investigated as flagging tests for the sensitive DNA recognition that can be utilized as a part of field applications to defeat restrictions. Gold nanoparticles (AuNPs) have been widely utilized due to its optical property and capacity to get functionalized with a mixed bag of biomolecules. This study exhibits the utilization of AuNPs functionalized with single-stranded oligonucleotide (AuNP-oligo test) for fast the identification of Human Papillomavirus (HPV). This test is displayed on interdigitated electrode sensor and supported by colorimetric assay. DNA conjugated AuNP has optical property that can be controlled for the applications in diagnostics. With its identification abilities, this methodology incorporates minimal effort, strong reagents and basic identification of HPV.
PURPOSE: In order to enhance cellular uptake and to facilitate transdermal delivery of DNA vaccine, polyamidoamine (PAMAM) dendrimers conjugated with HIV transactivator of transcription (TAT) was developed.
METHODS: First, the plasmid DNA (pIRES-H5/GFP) nanoparticle was formulated using PAMAM dendrimer and TAT peptide and then characterized for surface charge, particle size, DNA encapsulation and protection of the pIRES-H5/GFP DNA plasmid to enzymatic digestion. Subsequently, the potency of the TAT-conjugated dendrimer for gene delivery was evaluated through in vitro transfection into Vero cells followed by gene expression analysis including western blotting, fluorescent microscopy and PCR. The effect of the TAT peptide on cellular uptake of DNA vaccine was studied by qRT-PCR and flow cytometry. Finally, the ability of TAT-conjugated PAMAM dendrimer for transdermal delivery of the DNA plasmid was assessed through artificial membranes followed by qRT-PCR and flow cytometry.
RESULTS: TAT-conjugated PAMAM dendrimer showed the ability to form a compact and nanometre-sized polyplexes with the plasmid DNA, having the size range of 105 to 115 nm and a positive charge of +42 to +45 mV over the N/P ratio of 6:1(+/-). In vitro transfection analysis into Vero cells confirms the high potency of TAT-conjugated PAMAM dendrimer to enhance the cellular uptake of DNA vaccine. The permeability value assay through artificial membranes reveals that TAT-conjugated PAMAM has more capacity for transdermal delivery of the DNA compared to unmodified PAMAM dendrimer (P<0.05).
CONCLUSIONS: The findings of this study suggest that TAT-conjugated PAMAM dendrimer is a promising non-viral vector for transdermal use.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
Matched MeSH terms: Peptides/chemistry*; Polyamines/chemistry; Vaccines, DNA/chemistry*; Dendrimers/chemistry*; tat Gene Products, Human Immunodeficiency Virus/chemistry*
Current study employs mixture of chlorophyll-anthocyanin dye extracted from leaves of Cordyline fruticosa as new sensitizers for dye-sensitized solar cell (DSSCs), as well as betalains dye obtained from fruit of Hylocereus polyrhizus. Among ten pigments solvents, the ethanol and methanol extracts revealed higher absorption spectra of pigments extracted from C. fruticosa and H. polyrhizus respectively. A major effect of temperature increase was studied to increase the extraction yield. The results indicated that extraction temperature between 70 and 80°C exhibited a high dye concentration of each plant than other temperatures. The optimal temperature was around 80°C and there was a sharp decrease of dye concentration at temperatures higher than this temperature. According to experimental results, the conversion efficiency of DSSC fabricated by mixture of chlorophyll and anthocyanin dyes from C. fruticosa leaves is 0.5% with short-circuit current (Isc) of 1.3mA/cm-2, open-circuit voltage (Voc) of 0.62V and fill factor (FF) of 60.16%. The higher photoelectric conversion efficiency of the DSSC prepared from the extract of H. polyrhizus was 0.16%, with Voc of 0.5V, Isc of 0.4mA/cm-2 and FF of 79.16%. The DSSC based betalain dye extracted from fruit of H. polyrhizus shows higher maximum IPCE of 44% than that of the DSSCs sensitized with mixed chlorophyll-anthocyanin dye from C. fruticosa (42%).
Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.