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Commercially available ocular drug delivery systems are effective but less efficacious to manage diseases/disorders of the anterior segment of the eye. Recent advances in nanotechnology and molecular biology offer a great opportunity for efficacious ocular drug delivery for the treatments of anterior segment diseases/disorders. Nanoparticles have been designed for preparing eye drops or injectable solutions to surmount ocular obstacles faced after administration. Better drug pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, and biorecognition can be achieved to improve drug efficacy when drugs are loaded in the nanoparticles. Despite the fact that a number of review articles have been published at various points in the past regarding nanoparticles for drug delivery, there is not a review yet focusing on the development of nanoparticles for ocular drug delivery to the anterior segment of the eye. This review fills in the gap and summarizes the development of nanoparticles as drug carriers for improving the penetration and bioavailability of drugs to the anterior segment of the eye.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 122-18-9, molcular formula is C25H46ClN, introducing its new discovery. Recommanded Product: 122-18-9

Tear film alterations in dry eye disease (DED) include reduced tear volume and an increase in inflammatory cytokines. Instability and reduced tear production initiate a vicious cycle where hyperosmolarity, ocular inflammation, and apoptosis may induce damage of the ocular surface including keratitis. Topical cyclosporine (CsA) has been used for the treatment of moderate-to-severe DED; however, previous studies failed to demonstrate its benefits by the European Agency standards. A new formulation of CsA 0.1% has been recently approved in the EU to treat severe keratitis in DED patients. Patients with severe keratitis showed a better improvement after 6 months of treatment with CsA compared with vehicle. HLA-DR expression was significantly reduced by CsA treatment. The clinically significant improvement in keratitis associated with the inflammatory biomarker HLA-DR confirms the efficacy of CsA to improve inflammation and its damaging effect on the ocular surface in DED patients.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

Extracurricular laboratory:new discovery of N-Benzyl-N,N-dimethylhexadecan-1-aminium chloride

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Zwitterionic structures: From physicochemical properties toward computer-aided drug designs

Zwitterions, used widely in chemical, biological and medicinal fields, show distinct physicochemical properties relative to ordinary ampholytes, which largely decide their bioavailability and biological activities. In the present manuscript, these properties are discussed in order to facilitate our understanding of zwitterionic structures, followed by various examples of zwitterionic drugs and the critical role these properties play. We specifically focus our discussions on neuraminidase inhibitors (NAIs), which are used in the treatment and prevention of influenza, covering their computer-assisted design, transformation to zwitterionic isomers and interaction mechanisms of NAIs with proteins. The discovery and development of NAIs provide useful insights that may assist in the exploration of new zwitterionic drugs.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Preservatives in eyedrops: The good, the bad and the ugly

There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e., allergic, toxic, or inflammatory, as well as the respective roles of the active compound and the preservative in inducing the toxic and/or proinflammatory effects of ophthalmic solutions, is still being debated. The most frequently used preservative, benzalkonium chloride (BAK), has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies. As a quaternary ammonium, this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The mechanisms causing these effects have not been fully elucidated, although the involvement of immunoinflammatory reactions with the release of proinflammatory cytokines, apoptosis, oxidative stress, as well as direct interactions with the lipid components of the tear film and cell membranes have been well established. Preservative-induced adverse effects are therefore far from being restricted to only allergic reactions, and side effects are often very difficult to identify because they mostly occur in a delayed or poorly specific manner. Care should therefore be taken to avoid the long-term use of preservatives, otherwise a less toxic alternative to BAK should be developed, as this weakly allergenic but highly toxic compound exerts dose- and time-dependent effects. On the basis of all these experimental and clinical reports, it would be advisable to use benzalkonium-free solutions whenever possible, especially in patients with the greatest exposure to high doses or prolonged treatments, in those suffering from preexisting or concomitant ocular surface diseases, and those experiencing side effects related to the ocular surface. Indeed, mild symptoms should not be underestimated, neglected, or denied, because they may very well be the apparent manifestations of more severe, potentially threatening subclinical reactions that may later cause major concerns.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

Discovery of N-Benzyl-N,N-dimethylhexadecan-1-aminium chloride

The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 122-18-9 is helpful to your research. name: N-Benzyl-N,N-dimethylhexadecan-1-aminium chloride

In homogeneous catalysis, the catalyst is in the same phase as the reactant. The number of collisions between reactants and catalyst is at a maximum.In a patent, 122-18-9, name is N-Benzyl-N,N-dimethylhexadecan-1-aminium chloride, introducing its new discovery. name: N-Benzyl-N,N-dimethylhexadecan-1-aminium chloride

Quaternary ammonium compounds (e.g., benzalkonium chloride (BAC) and cetylpyridinium chloride (CPC)) constitute a group of cationic surfactants are widely used for personal hygiene and medical care despite the potential pulmonary toxicity. To examine whether BAC and CPC aerosols deposited in the alveolar region alter pulmonary function, we studied the effects on pulmonary surfactant using two-step in vitro models; cytotoxicity using A549 alveolar epithelial cell and changes in surface activity of the pulmonary surfactant monolayer using both Surfacten and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Cell viability was decreased with BAC and CPC dose-dependently. A comparison of cytotoxicity among BAC homologues with different length of alkyl chain showed that C16-BAC, which has the longest alkyl chain, was more cytotoxic than C12- or C14-BAC. Caspase-3/7 activity and cleaved form of caspase-3 and PARP were increased in BAC- and CPC-exposed cells. The elevated caspase-3/7 activity and their cleaved active forms were abolished by caspase-3-inhibitor. Furthermore, we examined the features of the surface pressure/trough area (pi-A) isotherm by the Langmuir-Wilhelmy method and atomic force microscopy (AFM) images of lipid monolayers on a subphase containing BAC, CPC, or pyridinium chloride (PC, as a control). The pi-A isotherms showed that addition of BAC or CPC yielded dose-dependent increases in surface pressure without compression, indicating that BAC and CPC expand the isotherm to larger areas at lower pressure. The collapse pressure diminished with increasing concentration of CPC. Topographic images indicated that BAC and CPC resulted in smaller condensed lipid domains compared to the control. Conversely, PC without hydrocarbon tail group, showed no cytotoxicity and did not change the isotherms and AFM images. These results indicate that BAC and CPC cause cell death via caspase-3-dependent apoptotic pathway in A549 cells and alter the alveolar surfactant activity. These effects can be attributed to the long alkyl chain of BAC and CPC.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

Extracurricular laboratory:new discovery of N-Benzyl-N,N-dimethylhexadecan-1-aminium chloride

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Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics

Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report the combination of hydrophilic-interaction liquid chromatography (HILIC) with traveling-wave IM-MS (TWIM-MS) for comprehensive lipidomics analysis. Main lipid categories such as glycerolipids, sphingolipids, and glycerophospholipids are separated on the basis of their lipid backbones in the IM dimension, whereas subclasses of each category are mostly separated on the basis of their headgroups in the HILIC dimension, demonstrating the orthogonality of HILIC and IM separations. Using our previously established lipid calibrants for collision cross-section (CCS) measurements in TWIM, we measured over 250 CCS values covering 12 lipid classes in positive and negative modes. The coverage of the HILICIM-MS method is demonstrated in the analysis of Neuro2a neuroblastoma cells exposed to benzalkonium chlorides (BACs) with C10 or C16 alkyl chains, which we have previously shown to affect gene expression related to cholesterol and lipid homeostasis. We found that BAC exposure resulted in significant changes to several lipid classes, including glycerides, sphingomyelins, phosphatidylcholines, and phosphatidylethanolamines. Our results indicate that BAC exposure modifies lipid homeostasis in a manner that is dependent upon the length of the BAC alkyl chain.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Macrocyclic compounds as amphiphile adaptors

In recent years, modulating amphiphilic assembly by macrocyclic receptors has been emerging as a fantastic topic. As we know, amphiphiles possess ability of self-assembly in aqueous solution due to their unique structures, resulting in important biological functions and various applications in our daily life and industry. Among methods to modulate their assembly behavior, using macrocyclic compounds as amphiphile adaptors owns advantages of convenience and efficiency. Preorganized structures and cavities of macrocyclic compounds enable them the ability of efficiently interacting with amphiphiles in different manners. These additional interactions alter amphiphilic assembly. In this review, we would like to provide a systemic summary of why and how macrocyclic compounds could behave as amphiphile adaptors. For this objective, we introduce related works from the viewpoint of intermolecular interaction. In general, addition of interactions which decrease electrostatic reputation of amphiphiles could promote amphiphilic assembly, and vice versa. Addition of interactions which prevent hydrophobic interaction could inhibit amphiphilc assembly. On the other hand, complexation of macromolecular compounds and amphiphiles could cause steric hindrance, which is unfavorable for assembly. We also take several classical amphiphiles as examples to clarify how different macrocyclic compounds adapt amphiphile assembly.

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Reference:
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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N-HALOGENATED AMINO ACID FORMULATIONS AND METHODS FOR CLEANING AND DISINFECTION

The present invention relates to methods for disinfecting or cleaning a contact lens comprising contacting a contact lens with a formulation comprising a N-halogenated amino acid and a phase transfer agent for a time sufficient to disinfect or clean the lens. This specification further discloses a formulation for disinfecting a contact lens comprising an N-halogenated amino acid and a phase transfer agent.

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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Cross-inhibition of pathogenic agents and the host proteins they exploit

The major limitations of pathogen-directed therapies are the emergence of drug-resistance and their narrow spectrum of coverage. A recently applied approach directs therapies against host proteins exploited by pathogens in order to circumvent these limitations. However, host-oriented drugs leave the pathogens unaffected and may result in continued pathogen dissemination. In this study we aimed to discover drugs that could simultaneously cross-inhibit pathogenic agents, as well as the host proteins that mediate their lethality. We observed that many pathogenic and host-assisting proteins belong to the same functional class. In doing so we targeted a protease component of anthrax toxin as well as host proteases exploited by this toxin. We identified two approved drugs, ascorbic acid 6-palmitate and salmon sperm protamine, that effectively inhibited anthrax cytotoxic protease and demonstrated that they also block proteolytic activities of host furin, cathepsin B, and caspases that mediate toxin’s lethality in cells. We demonstrated that these drugs are broad-spectrum and reduce cellular sensitivity to other bacterial toxins that require the same host proteases. This approach should be generally applicable to the discovery of simultaneous pathogen and host-targeting inhibitors of many additional pathogenic agents.

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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI

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Spectroscopic and time-resolved fluorescence emission properties of a cationic and an anionic porphyrin in biomimetic media and Candida albicans cells

Spectroscopic and time-resolved fluorescence emission techniques were used to provide information for the interaction of 5,10,15,20-tetrakis(4-N,N,N- trimethylammoniumphenyl) porphyrin (TMAP4+) and 5,10,15,20- tetrakis(4-sulphonatophenyl) porphyrin (TPPS4-) with different biomimetic media and with Candida albicans cells. In n-heptane/sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/water and benzene/benzyl-n- hexadecyldimethylammonium chloride (BHDC)/water reverse micelles interactions were dependent on the micellar interface and the amount of water dispersed in the microemulsion. It was also observed that the DNA binding of cationic porphyrin TMAP4+ led to two lifetimes. In vitro investigations showed that TMAP4+ is bound to C. albicans. Fluorescence lifetime measurements and fluorescence microscopic images provided additional insight into the effects of porphyrin uptake by cells. The results reveal a double localization of TMAP4+ inside of C. albicans cells. Thus, a redistribution of TMAP4+ was observed in unwashed cells, probably due to a relocalisation of molecules that were weakly bound to the cells or remained in solution. However, this effect was not found with molecules tightly bound in the cells, after one washing step.

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Reference£º
Metal catalyst and ligand design,
Ligand Template Strategies for Catalyst Encapsulation – NCBI