Display omitted
•A novel photocatalyst (30 % Ag2WO4/PCN) was successfully synthesized.•The photocatalyst showed remarkable photocatalytic activity under visible-light.•O2– was the main reactive ...species in the IDM photocatalytic degradation.•The mechanism for IDM degradation by the 30 % Ag2WO4/PCN was proposed.
As a metal-free photocatalyst, the photocatalytic activity of graphitic carbon nitride (g-C3N4) remains restricted due to an insufficient visible-light absorption capacity, the rapid recombination of photoinduced carriers, and low surface area. Consequently, P-doped g-C3N4 (PCN) was successfully prepared via a single -step thermal polymerization technique using phytic acid biomass and urea, which exhibited remarkable photocatalytic activity for the degradation of indometacin (IDM). The IDM degradation rate was 7.1 times greater than that of pristine g-C3N4 (CN). Furthermore, Ag2WO4 was loaded onto the surface of the PCN, which formed a Z-scheme heterostructure that promoted the separation of photogenerated carriers. According to analyses of the chemical binding states of PCN, P atoms replaced carbon atoms in the CN framework. According to electron localization function analysis, the low ELF values of P-N facilitated the transfer of photoelectrons. The results of active species scavenging experiments confirmed that superoxide radicals were the primary active species in the photocatalytic degradation system. Finally, the photocatalytic degradation pathways of IDM were predicted through the identification of by-products and IDM reaction sites.
•Degradation of indometacin by plasma oxidation and DBPs formation were assessed.••OH, O2•−, and 1O2 in the plasma were responsible for indometacin decomposition.•Possible decomposition pathways of ...indometacin by plasma oxidation were proposed.•Formation and toxicity of HAAs rose after degradation, but decreased for N-DBPs.•Relevant roadmaps among DBPs and degradation intermediates were figured out.
Indometacin (IDM), as a kind of non-steroidal anti-inflammatory drugs, has ecological and health risks, which is the potential precursor of chlorination disinfection byproducts (DBPs). Non-thermal discharge plasma was attempted to eliminate IDM and control subsequent DBPs formation. Satisfactory removal performance for IDM was realized by the plasma oxidation; almost 100% of IDM was removed within 2 min. Relatively greater removal efficiency was gained at a higher plasma voltage and a lower pH level. Electron paramagnetic resonance spectrometer revealed that reactive species ·OH, O2·−, and 1O2 were responsible for IDM decomposition. Based on analyses of Fourier transform infrared spectroscopy, two-dimensional correlation spectroscopy, three-dimensional fluorescence spectrum, and gas chromatography-mass spectrometer, attacks of reactive species resulted in sequence breakages in functional groups of IDM, leading to production of small molecular alcohols, acids, and amines. Possible decomposition pathways of IDM were proposed. The produced acetamide and 1H-indol-5-ol were important precursors of DBPs. Formation and toxicity of nitrogen-containing DBPs were dramatically inhibited after IDM degradation; however, those of haloacetic acids were strengthened. The relevant roadmaps among DBPs and degradation intermediates were figured out. This study revealed the underlying mechanisms of IDM degradation by discharge plasma and its potential risks in chlorination disinfection.
Display omitted
Abstract
Background
Paroxysmal hemicrania and hemicrania continua are indometacin-sensitive trigeminal autonomic cephalalgias, a terminology which reflects the predominant distribution of the pain, ...observable cranial autonomic features and shared pathophysiology. Understanding the latter is limited, both by low prevalence and the intricacies of studying brain function, requiring multimodal techniques to glean insights into such disorders. Similarly obscure is the curious response to indometacin. This review will address what is currently known about pathophysiology, the rationale for the current classification and, features which may confound the diagnosis, such as lack of cranial autonomic symptoms and those which are typically associated with migraine such as nausea, photophobia, phonophobia and aura. Despite these characteristics, a dramatic response to indometacin, which is not seen in migraine nor the other trigeminal autonomic cephalalgias , provides the hallmark of the diagnosis. The main clinical differential for paroxysmal hemicrania is based on temporal pattern and lies between cluster headache and short-lasting-neuralgiform headache attacks with tearing or additional cranial autonomic symptoms. For hemicrania continua it is more challenging as the main differential for which the disorder is often treated is migraine. A prior episodic pattern, often days at a time, and the tendency to exacerbation with analgesics will further deflect from the diagnosis. The relevance of this is that there is little overlap in therapeutics between paroxysmal hemicrania and hemicrania continua and other headache disorders and there are limited effective alternatives to indometacin. The most effective are other non-steroidal anti-inflammatory drugs including the newer COX-II inhibitors. Even though early reports suggest that a higher indometacin dose-requirement may herald a secondary precipitating pathology, this does not seem to be the case, with syndrome and response to treatment being similar with the primary disorder. In this context imaging of new onset paroxysmal hemicrania or hemicrania continua and implication of the results will be discussed as will alternative treatment options.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Display omitted
•The novel chiral silicon coupling agents (TESPSA-L/D-Pro) were prepared successfully.•Chiral microenvironment-responsive mesoporous silica nanoparticles (CMR-L/D-MSN) with ...molecular-level chirality were prepared successfully.•CMR-L/D-MSN had high specific surface area and exhibited the potential the chiral recognition function.•CMR-D-MSN had higher bioavailability and stronger anti-inflammatory effect for delivering IMC compare with CMR-L-MSN.
The purpose of this study was to investigate the potential chiral recognition functions induced by two kinds of novel chiral microenvironment-responsive mesoporous silica nanoparticles (CMR-L-MSN and CMR-D-MSN) for the oral delivery of the poorly water-soluble achiral drug indomethacin (IMC). The as-synthesized CMR-L-MSN and CMR-D-MSN with molecular chirality and high specific surface area (SBET: 1141 and 1075 m2/g, respectively) were successfully prepared through grafting chiral molecular functional groups. The characterization results showed that CMR-L-MSN and CMR-D-MSN were spherical nanoparticles with opposite chiral features and clearly visible pore channels. Meanwhile, they exhibited good biosafety and degradability. In vitro drug release study indicated that both CMR-L-MSN and CMR-D-MSN significantly improved IMC dissolution compared with naked-MSN (N-MSN) (p < 0.05) and exhibited different chiral recognition functions for drug release in the simulated chiral environments in vitro (pH 6.8 PBS-D/L), in which CMR-D-MSN could be triggered by the L-configurations in chiral environments and exhibited a better drug release effect. As expect, the results of in vivo biological effects disclosed that CMR-D-MSN had higher bioavailability of IMC and obvious advantages on drug adsorption and in vivo distribution, and exerted stronger anti-inflammatory effect after making specific response to the in vivo chiral environment.
Display omitted
•Biocompatible and biodegradable L/d-BPEIN-MSX with chiral surface topology was constructed through a facile, economical, and biomimetic strategy within 2 min.•L/d-BPEIN-MSX could in ...situ encapsulated and endowed chirality to the guest molecules.•d-BPEIN-MSX had favorable chiral recognized release manners, while l-BPEIN-MSX exhibited beneficial behaviors in bio-processes related to oral adsorption.•The study proposed a universal strategy on overcoming cargo packaging and release, improving the oral adsorption and reducing the gastrointestinal side effect of drug.
Driven by the clinical demand on improving the oral bioavailability and reducing the side effects of insoluble drug, aminoated mesoporous silica xerogel (named L/d-BPEIN-MSX) with chiral surface topology was constructed through a facile, economical, and biomimetic strategy within 2 min, and served as the carrier of indomethacin (IMC). In the synthetic process, L/d-tartaric acid (L/d-TA) self-assembled with branched polyethyleneimine (BPEI) to endow chirality and synergistic promoted silica deposition, while 3-aminopropyl triethoxysilane (APTES) polycondensated with the silica source to form aminoated mesostructure. By premixed strategy, IMC can be in situ loaded into L/d-BPEIN-MSX with high efficiency, which then became active in circular dichroism (CD) spectra owing to induced chirality. Noteworthy, IMC-L/d-BPEIN-MSX significantly improved the release rate of IMC with multiple controlled release manners. That is, d-BPEIN-MSX had favorable drug release behavior which could respond to the chiral stimuli, whereas l-BPEIN-MSX exhibited advantageous chiral surface topology that was beneficial for bio-processes related to oral adsorption. Undoubtedly, they increased the bioavailability of IMC to 8–9 times, displayed good anti-inflammatory effect, and reduced the gastrointestinal irritation of IMC. In addition, L/d-BPEIN-MSX had low toxicity and irritation, and was proven to be biodegradable and biocompatible, which could meet the requirement for biomedical applications.
Display omitted
The aim of this work was to investigate the efficient targeting and delivery of indometacin (IND), as a model anti-inflammatory drug to the colon for treatment of inflammatory bowel ...disease. We prepared fast disintegrating tablets (FDT) containing IND encapsulated within poly(glycerol-adipate-co-ɷ-pentadecalactone), PGA-co-PDL, microparticles and coated with Eudragit L100-55 at different ratios (1:1.5, 1:1, 1:0.5). Microparticles encapsulated with IND were prepared using an o/w single emulsion solvent evaporation technique and coated with Eudragit L-100-55 via spray drying. The produced coated microparticles (PGA-co-PDL-IND/Eudragit) were formulated into optimised FTD using a single station press. The loading, in vitro release, permeability and transport of IND from PGA-co-PDL-IND/Eudragit microparticles was studied in Caco-2 cell lines. IND was efficiently encapsulated (570.15±4.2μg/mg) within the PGA-co-PDL microparticles. In vitro release of PGA-co-PDL-IND/Eudragit microparticles (1:1.5) showed significantly (p<0.05, ANOVA/Tukey) lower release of IND 13.70±1.6 and 56.46±3.8% compared with 1:1 (89.61±2.5, 80.13±2.6%) and 1:0.5 (39.46±0.9 & 43.38±3.12) after 3 and 43h at pH 5.5 and 6.8, respectively. The permeability and transport studies indicated IND released from PGA-co-PDL-IND/Eudragit microparticles had a lower permeability coefficient of 13.95±0.68×10−6cm/s compared to free IND 23.06±3.56×10−6cm/s. These results indicate the possibility of targeting anti-inflammatory drugs to the colon using FDTs containing microparticles coated with Eudragit.
Display omitted
•The On-Off-D/ L-CMSN were successfully composed.•The grafting groups distributed the inner and outer surfaces of On-Off-D/ L-CMSN.•On-Off-D/ L-CMSN can trigger chiral biological ...environment to achieve chiral recognition functions.
In the current stage, the On-Off mechanism of chiral mesoporous silica nanoparticles (CMSN) for delivering achiral drug in chiral environment has rarely been reported. Herein, On-Off chiral mesoporous silica nanoparticles (On-Off-D-CMSN and On-Off-L-CMSN) were successfully synthesized and its particular contribution in delivering achiral drug indometacin (IMC) in chiral environment was mainly studied. The as-synthesized On-Off-D-CMSN and On-Off-L-CMSN were verified by fourier transform infrared spectrometer and circular dichroism. The transmission electron microscope test and nitrogen adsorption/desorption analysis showed that On-Off-D-CMSN and On-Off-L-CMSN were regular spheres with concealed pore channels. The zeta potential analysis demonstrated that the grafting functional groups distributed on the inner and outer surfaces of On-Off-D-CMSN and On-Off-L-CMSN. Through dissolution experiment, the drug release of IMC loaded On-Off-D-CMSN (84%) and IMC loaded On-Off-L-CMSN (70%) were about 2.4 and 2.0 times higher than pure IMC (35%) in pH 6.8 phosphate buffer solution (PBS), respectively. IMC loaded On-Off-D-CMSN and IMC loaded On-Off-L-CMSN exerted different chiral recognition functions with On-Off mechanism in in-vitro chiral environment (pH 6.8 PBS-L and pH 6.8 PBS-D). The results of anti-inflammation pharmacodynamics further demonstrated that On-Off-D-CMSN and On-Off-L-CMSN can trigger chiral biological environment to achieve on or off chiral recognition functions. The unique advantages of On-Off chiral mesoporous silica nanoparticles in triggering chiral biological environment can provide valuable instruction for designing drug delivery system.
PDF
