[Study on Factors Affecting Hemolytic Properties of Cyanoacrylate Glues for Surgical Use].

This study aims to discuss the factors affecting the hemolytic properties of α-cyanoacrylate glues for surgical use. The results showed that the different extractions, test methods, pH value, rapid solidification and the extract ratio were the main factors affecting the hemolytic properties. The choose of PBS as the extraction for haemolysis test maybe was more suitable than physiological saline. It was recommended that using both direct contact methods and indirect contact methods should be more comprehensive for hemolytic evaluation.

Degradation of polymer banknotes through handling, and effect on fingermark visualisation.

The surface structure of mint (as-issued) and handled polymer five pounds sterling banknotes was studied by atomic force microscopy and laser scanning confocal microscopy. A total of 1856 fingermarks on mint and handled banknotes from four different issuing banks (Bank of England, Bank of Scotland, Royal Bank of Scotland and Clydesdale Bank) were visualised with Vacuum Metal Deposition (VMD), Cyanoacrylate Fuming (CAF) and, on Clydesdale Bank notes, magnetic fluorescent powder. VMD was significantly more effective in developing fingermarks on handled banknotes, across all the banks studied, although effectiveness varied with issuing bank. For example, on handled Bank of England notes 45% of marks showed ridge detail with VMD development and 28% with CAF; for Bank of Scotland handled notes success rates were 17% with VMD and 1% with CAF. Microscopy of degraded banknotes showed the loss of intaglio printing and the formation of a cracked surface structure in the handled notes. These features can lead to the trapping of powder, or contaminants, increasing quantity of development agent in fingermark background between the ridges, decreasing contrast and decreasing performance of powder-based fingermark development techniques. These same features can restrict the migration of components of the fingermark, preventing fingermarks degrading through spread of material and thus reducing potential formation of empty prints, so that VMD development is not adversely affected.

Polymerization Enhancers for Cyanoacrylate Skin Adhesive.

Cyanoacrylate glues are a renowned synthetic tissue sealant that cures rapidly through polymerization at room temperature, felicitating medical glues to treat skin wounds and surgical openings. Despite a wide range of cyanoacrylates available, only 2-octyl cyanoacrylates (OCA) provides the best biocompatibility. In this study, the polymerization and adhesive properties of 2-octyl cyanoacrylates (OCA) are explored in the presence of a highly biocompatible and biochemically inert polymer, poly(ethylene glycol) polyhedral oligomeric silsesquioxane (PEG-POSS). The effect of PEG-POSS on the polymerization of OCA is examined on a plastic surface and over pig skin. A peel-test is performed to evaluate the strength of OCA adhesive properties between two pieces of pig skin samples. Additionally, thin films of OCA are prepared using different fillers and evaluated for tear test. The results reveal that when applied on the plastic or pig skin, PEG-POSS initiated polymerization in OCA yields a high molecular weight OCA polymer with much better adhesive properties compared to commercially available cyanoacrylate adhesives. The relative change in the molecular weights of OCA compared to commercially available cyanoacrylate bioadhesives such as Dermaflex is much higher. The pig skin peeling test shows that OCA needs higher peeling force than Dermaflex.

Ultra-strong bio-glue from genetically engineered polypeptides.

The development of biomedical glues is an important, yet challenging task as seemingly mutually exclusive properties need to be combined in one material, i.e. strong adhesion and adaption to remodeling processes in healing tissue. Here, we report a biocompatible and biodegradable protein-based adhesive with high adhesion strengths. The maximum strength reaches 16.5 ± 2.2 MPa on hard substrates, which is comparable to that of commercial cyanoacrylate superglue and higher than other protein-based adhesives by at least one order of magnitude. Moreover, the strong adhesion on soft tissues qualifies the adhesive as biomedical glue outperforming some commercial products. Robust mechanical properties are realized without covalent bond formation during the adhesion process. A complex consisting of cationic supercharged polypeptides and anionic aromatic surfactants with lysine to surfactant molar ratio of 1:0.9 is driven by multiple supramolecular interactions enabling such strong adhesion. We demonstrate the glue's robust performance in vitro and in vivo for cosmetic and hemostasis applications and accelerated wound healing by comparison to surgical wound closures.

Reversible covalent inhibitors suppress enterovirus 71 infection by targeting the 3C protease.

As one of the principal etiological agents of hand, foot, and mouth disease (HFMD), enterovirus 71 (EV71) is associated with severe neurological complications or fatal diseases, while without effective medications thus far. Here we applied dually activated Michael acceptor to develop a series of reversible covalent compounds for EV71 3C protease (3Cpro), a promising antiviral drug target that plays an essential role during viral replication by cleaving the precursor polyprotein, inhibiting host protein synthesis, and evading innate immunity. Among them, cyanoacrylate and Boc-protected cyanoarylamide derivatives (SLQ-4 and SLQ-5) showed effective antiviral activity against EV71. The two inhibitors exhibited broad antiviral effects, acting on RD, 293T, and Vero cell lines, as well as on EV71 A, B, C, CVA16, and CVB3 viral strains. We further determined the binding pockets between the two inhibitors and 3Cpro based on docking studies. These results, together with our previous studies, provide evidence to elucidate the mechanism of action of these two reversible covalent inhibitors and contribute to the development of clinically effective medicines to treat EV71 infections.

An improved method for preparation of mouse retinal cryosections.

Immunohistochemistry using mouse retinal cryosections is a routine assay used in vision research. However, retinal tissues are fragile, and it is difficult to obtain an ideal retinal cryosection. Here, we developed a modified method for preparing retinal cryosection. Super Glue was applied on the surface of the sclera before the cornea and the lens are removed from either the unfixed or PFA-fixed mouse eyeballs. The new methods largely prevented retinal detachment in mouse retinal cryosections. Immunostaining of retinal cryosections derived from PFA-fixed mouse eyes using rod and cone markers yielded high-quality immunofluorescent images. Immunolabeling of retinal cryosections obtained from unfixed mouse eyes using a cilium-specific marker had improved orientations of photoreceptor connecting cilia. This new method substantially improves the morphology and immunostaining results of fixed and unfixed mouse eyes.

Current role of cyanoacrylate glue transcatheter embolization in the treatment of acute nonvariceal gastrointestinal bleeding.

INTRODUCTION: Over the past three decades, transcatheter arterial embolization (TAE) has become the first-line therapy for the management of acute nonvariceal gastrointestinal bleeding (NVGIB) that is refractory to endoscopic hemostasis. Advances in catheter-based techniques and newer liquid embolic agents, as well as recognition of the effectiveness of minimally invasive treatment options, have expanded the role of interventional radiology in the treatment of acute NVGIB. Many embolic agents have been used successfully. However, no guidelines exist about the choice of the best embolic agent which is still controversial. Cyanoacrylate glue has gained acceptance over time. This article aims to address the current role of TAE using cyanoacrylate glue for the treatment of acute NVGIB. AREAS COVERED: The authors undertook a literature review of the current evidence on the use of cyanoacrylate glue in treating patients with acute NVGIB. EXPERT OPINION: The evidence shows that cyanoacrylate glue is the most clinically useful embolic agent in treating patients with acute NVGIB, despite the need for learning curve, especially in case of coagulopathy. At present, research is ongoing to assess liquid embolic agents in the treatment of patients presenting with acute NVGIB. More research is needed but cyanoacrylate glue show promise for the future.

Structural basis of Fusarium myosin I inhibition by phenamacril.

Fusarium is a genus of filamentous fungi that includes species that cause devastating diseases in major staple crops, such as wheat, maize, rice, and barley, resulting in severe yield losses and mycotoxin contamination of infected grains. Phenamacril is a novel fungicide that is considered environmentally benign due to its exceptional specificity; it inhibits the ATPase activity of the sole class I myosin of only a subset of Fusarium species including the major plant pathogens F. graminearum, F. asiaticum and F. fujikuroi. To understand the underlying mechanisms of inhibition, species specificity, and resistance mutations, we have determined the crystal structure of phenamacril-bound F. graminearum myosin I. Phenamacril binds in the actin-binding cleft in a new allosteric pocket that contains the central residue of the regulatory Switch 2 loop and that is collapsed in the structure of a myosin with closed actin-binding cleft, suggesting that pocket occupancy blocks cleft closure. We have further identified a single, transferable phenamacril-binding residue found exclusively in phenamacril-sensitive myosins to confer phenamacril selectivity.

Molecular Staples for Tough and Stretchable Adhesion in Integrated Soft Materials.

The integration of soft materials-biological tissues, gels, and elastomers-is a rapidly developing technology of this time. Whereas hard materials are adhered using adhesives of hard polymers since antiquity, these hard polymers are generally unsuited to adhere soft materials, because hard polymers constrain the deformation of soft materials. This paper describes a design principle to use hard polymers to adhere soft materials, such that adhesion remains tough after the adhered soft materials are subject to many cycles of large stretches in the plane of their interface. The two soft materials have stretchable polymer networks, but need not have functional groups for adhesion. The two soft materials are adhered by forming, in situ at their interface, islands of a hard polymer. The adhesion is tough if the islands themselves are strong, and the polymers of the islands are in topological entanglement with the polymer networks of the soft materials. The adhesion is stretchable if the islands are smaller than the flaw sensitivity length. Several methods of forming the hard polymer islands are demonstrated, and the mechanics and chemistry of adhesion are studied. The design principle will enable many hard polymers to form tough and stretchable adhesion between soft materials.

Effect of thienyl units in cyanoacrylic acid derivatives toward dye-sensitized solar cells.

A series of heterocyclic donor-acceptor systems were synthesized and well characterized by using 1H, 13C NMR, FT-IR, and elemental analysis. They were designed to investigate the effect of thiophene and cyanoacrylic acid number units on the thermal, optical, electrochemical and finally photovoltaic properties of dye-sensitized solar cells prepared with the selected compounds. The effect of chemical structure on their properties was demonstrated. They showed the beginning of thermal decomposition between 230 and 270 °C. The compounds absorbed the radiation in the range of 300-500 nm or 200-400 nm. They were electrochemically active and varied in energy band gap from 3.40 to 1.58 eV. Additionally, their optimized geometry, HOMO-LUMO levels, ionization potential, and electron affinity were evaluated using density functional theory. The photovoltaic devices based on TiO2 sensitized with the obtained molecules exhibited low power conversion efficiency, which was the highest for the device containing the symmetrical molecule with bithiophene structure. Under co-sensitization, the cell made of the same compound gave significant enhancement of efficiency of 6.3% being higher to that of the individual device prepared from dye N719 (5.75%). Moreover, the effects of immersion time of TiO2 electrode in the dye solution and co-sensitization methods were tested. The surface morphology of photoanode was investigated using atomic force microscopy.

Fast Approach to the Hydrophobization of Bacterial Cellulose via the Direct Polymerization of Ethyl 2-Cyanoacrylate.

Bacterial cellulose (BC) has a broad range of applications in biomedical fields and cosmetics. Applied as wound dressing, BC tends to stick to the sore especially upon drying, and hydrophobization improves its performance in this regard. This article reports a facile and rapid yet a highly efficient approach for BC hydrophobization through direct polymerization of ethyl 2-cyanoacrylate on the BC fibers. The modified material preserves the favorable porous structure of the matrix material while displaying significantly higher hydrophobicity and significantly decreased stickiness to the wound. The BC surface can be modified in 15 min. Overall, this can be considered a ready-to-apply approach for the fabrication of BC wound dressings with enhanced performance. The modification was demonstrated to improve the material's biocompatibility and to introduce antimicrobial activity (immortalized human fibroblast assay).

Application of Dually Activated Michael Acceptor to the Rational Design of Reversible Covalent Inhibitor for Enterovirus 71 3C Protease.

Targeted covalent inhibitors (TCIs) have attracted growing attention from the pharmaceutical industry in recent decades because they have potential advantages in terms of efficacy, selectivity, and safety. TCIs have recently evolved into a new version with reversibility that can be systematically modulated. This feature may diminish the risk of haptenization and help optimize the drug-target residence time as needed. The enteroviral 3C protease (3Cpro) is a valuable therapeutic target, but the development of 3Cpro inhibitors is far from satisfactory. Therefore, we aimed to apply a reversible TCI approach to the design of novel 3Cpro inhibitors. The introduction of various substituents onto the α-carbon of classical Michael acceptors yielded inhibitors bearing several classes of warheads. Using steady-state kinetics and biomolecular mass spectrometry, we confirmed the mode of reversible covalent inhibition and elucidated the mechanism by which the potency and reversibility were affected by electronic and steric factors. This research produced several potent inhibitors with good selectivity and suitable reversibility; moreover, it validated the reversible TCI approach in the field of viral infection, suggesting broader applications in the design of reversible covalent inhibitors for other proteases.

Poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) as possible agents in tumor treatment.

Tumor eradication has many challenges due to the difficulty of selectively delivering anticancer drugs to malignant cells avoiding contact with healthy tissues/organs. The improvement of antitumor efficacy and the reduction of systemic side effects can be achieved using drug loaded nanoparticles. In this study, poly (ethyl 2-cyanoacrylate) nanoparticles (PECA-NPs) were prepared using an emulsion polymerization method and their potential for cancer treatment was investigated. The size, polydispersity index and zeta potential of prepared nanoparticles are about 80 nm, 0.08 and -39.7 mV, respectively. The stability test shows that the formulation is stable for 15 days, while an increase in particle size occurs after 30 days. TEM reveals the spherical morphology of nanoparticles; furthermore, FTIR and 1H NMR analyses confirm the structure of PECA-NPs and the complete polymerization. The nanoparticles demonstrate an in vitro concentration-dependent cytotoxicity against human epithelial colorectal adenocarcinoma cell lines (Caco-2), as assessed by MTT assay. The anticancer activity of PECA-NPs was studied on 3D tumor spheroids models of hepatocellular carcinoma (HepG2) and kidney adenocarcinoma cells (A498) to better understand how the nanoparticles could interact with a complex structure such as a tumor. The results confirm the antitumor activity of PECA-NPs. Therefore, these systems can be considered good candidates in tumor treatment.

A journey through the emergence of nanomedicines with poly(alkylcyanoacrylate) based nanoparticles.

Starting in the late 1970s, the pioneering work of Patrick Couvreur gave birth to the first biodegradable nanoparticles composed of a biodegradable synthetic polymer. These nanoparticles, made of poly(alkylcyanoacrylate) (PACA), were the first synthetic polymer-based nanoparticulate drug carriers undergoing a phase III clinical trial so far. Analyzing the journey from the birth of PACA nanoparticles to their clinical evaluation, this paper highlights their remarkable adaptability to bypass various drug delivery challenges found on the way. At present, PACA nanoparticles include a wide range of nanoparticles that can associate drugs of different chemical nature and can be administered in vivo by different routes. The most recent technologies giving the nanoparticles customised functions could also be implemented on this family of nanoparticles. Through different examples, this paper discusses the seminal role of the PACA nanoparticles' family in the development of nanomedicines.

From poly(alkyl cyanoacrylate) to squalene as core material for the design of nanomedicines.

This review article covers the most important steps of the pioneering work of Patrick Couvreur and tries to shed light on his outstanding career that has been a source of inspiration for many decades. His discovery of biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) has opened large perspectives in nanomedicine. Indeed, NPs made from various types of alkyl cyanoacrylate monomers have been used in different applications, such as the treatment of intracellular infections or the treatment of multidrug resistant hepatocarcinoma. This latest application led to the Phase III clinical trial of Livatag®, a PACA nanoparticulate formulation of doxorubicin. Despite the success of PACA NPs, the development of a novel type of NP with higher drug loadings and lower burst release was tackled by the discovery of squalene-based nanomedicines where the drug is covalently linked to the lipid derivative and the resulting conjugate is self-assembled into NPs. This pioneering work was accompanied by a wide range of novel applications which mainly dealt with the management of unmet medical needs (e.g. pancreatic cancer, brain ischaemia and spinal cord injury).

[Evaluation of the Cytotoxicity of Commercially Available Nail Adhesives].

Nail tips are nail art materials that can be attached to the nail with adhesives. Recently, nail/finger injuries related to nail tips have been reported and one of the causes is considered to be the adhesives used for attaching nail tips. The components of nail adhesives are mostly cyanoacrylate, which is also used as an industrial instant adhesive. During curing, cyanoacrylate adhesives release formaldehyde through hydrolysis. When it is marketed as a nail adhesive, there is no regulation regarding its formaldehyde amount nor obligation to indicate its ingredients in Japan. Additionally, a biological safety test is not required for nail adhesives. Thus, because the safety of nail adhesives is inadequately confirmed, it is necessary to investigate their biological safety. Therefore, we purchased 5 commercially available nail adhesives and 1 medical adhesive and examined their formaldehyde content and cytotoxicity. We examined the cytotoxicity of the adhesives in V79 cells by a colony forming assay. In this test, 5 nail adhesives showed higher toxicity than 1 medical adhesive. Formaldehyde concentrations in the extract of adhesives were as follows: 17.5 to 24.2 µg/mL for nail adhesives and 7.4 µg/mL for medical adhesives. Cyanoacetate did not elicit cytotoxicity at the final concentration up to 1000 µM. However, formaldehyde showed cytotoxicity, with an IC50 of 79 µM (2.4 µg/mL). Taken together, the cytotoxicity of nail adhesives could be due to the formaldehyde generated by the hydrolysis of cyanoacrylate. It seems important that nail adhesives will be regulated by obligation and enhanced safety in the future.

Novel polymeric biomaterial poly(butyl-2-cyanoacrylate) nanowires: synthesis, characterization and formation mechanism.

Poly(butyl-2-cyanoacrylate) (PBCA) nanoparticles have been widely elaborated for nearly half a century. However, PBCA nanowires (PNWs) were seldom investigated. Here, new polymeric biomaterial PNWs were prepared via emulsion polymerization based on the sodium dodecyl sulfate (SDS)-assisted emulsion process. Results indicated that SDS micelles and PBCA polymer can develop surfactant-polymer complexes by self-assembly at room temperature. SDS concentration was confirmed to be the critical parameter for the association of the surfactant and the polymer. With the addition of SDS (0-40 mM), the interaction between SDS and PBCA led to a series of transitions from nanoparticles to nanowires. These morphology transitions were triggered by changing the electrostatic repulsion in the SDS-PBCA system, confirmed by the variety of zeta potential with increasing molar contents of SDS. To overcome the electrostatic repulsion, the complexes underwent transitions from spherical, worm-like (short-cylindrical), to elongated-cylindrical form. Finally, associated with the results from scanning / transmission electron microscopy (SEM / TEM), the elongated-cylindrical PNWs acquired at 20 mM of SDS were chosen to execute cell viability assay, which showed that they had no toxicity but with good-biocompatibility at the doses ≤ 50 µg/ml. These results indicate that the PNWs prepared by this facile-green and low-toxic strategy can potentially work as promising biomaterials in the biomedicine field.

Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway.

A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 µM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.

Promoting Immune Efficacy of the Oral Helicobacter pylori Vaccine by HP55/PBCA Nanoparticles against the Gastrointestinal Environment.

The immunogenicity of oral subunit vaccines is poor partly as a result of the harsh milieu of the gastrointestinal (GI) tract. For some pathogens that restrictedly inhabit the GI tract, a vaccine that works in situ may provide more potent protection than vaccines that operate parenterally. Yet, no appropriate delivery system is available for oral subunit vaccines. In this study, we designed HP55/poly( n-butylcyanoacrylate) (PBCA) nanoparticles (NPs) to carry Helicobacter pylori ( H. pylori) subunit vaccine CCF for oral administration in a prophylactic mice model. These NPs, which are synthesized using an interfacial polymerization method, protected the CCF antigen not only from the acidic pH in simulated gastric fluid (SGF, pH 1.2) but also from the proteolysis in simulated intestinal fluid (SIF, pH 7.4). Oral vaccination of mice with HP55/PBCA-CCF NPs promoted the production of serum antigen-specific antibodies, mucosal secretory IgA, and proinflammatory cytokines. Moreover, a Th1/Th17 response and augmented lymphocytes were found in the gastric tissue of HP55/PBCA-CCF NP-immunized mice, which might eventually limit H. pylori colonization. Collectively, these results indicate that HP55/PBCA NPs are promising carriers against the severe situation of the GI tract and thereby may be further utilized for other orally administrated vaccines or drugs.