Benzocaine Research Articles

Controlled ROMP synthesis of side-chain ferrocene and adamantane-containing diblock copolymer for the construction of redox-responsive micellar carriers

We present the controlled synthesis of the polynorbornene-based well-defined block copolymer PNFc-b-PNAd side-chain containing ferrocene (Fc) and adamantane (Ad) units by the ring-opening metathesis polymerization using the 3rd generation Grubbs catalyst. A polycationic amphiphilic block copolymer PNFcium-b-PNAd was then fabricated by the stoichiometric oxidation of Fc into ferricinium (Fcium) cations, and its redox-controlled reversible self-assembly behavior in water was demonstrated by SEM and DLS with glutathione as reductant and FeCl3 as oxidant. By using benzocaine (BA) as model cargo, the loading ability of the cationic micelles formed by PNFcium-b-PNAd was investigated and confirmed, and the reduction of Fcium could lead to the rapid release of loaded payloads. A new supramolecular copolymer PNFc-b-PNAd@β-CD was further prepared by simply mixing PNFc-b-PNAd and β-cyclodextrin (β-CD) with equimolar quantity to Ad units, in which host-guest interactions were mainly observed between β-CD and pendant Ad. Owing to the formation of hydrophilic inclusion complexes, PNFc-b-PNAd@β-CD possesses amphiphilic property and exhibits redox-controlled self-assembly behavior in water, too. The oxidation-triggered release of loaded-BA from the supramolecular micelles was observed in a slow and durable way. The present novel redox-responsive micelles provide innovative examples of rational design for stimuli-responsive carriers by using Fc-containing polymers.

EFFICACY OF THORACIC PARAVERTEBRAL BLOCK ANESTHESIA IN BREAST AUGMENTATION SURGERY.

08Sep 2018 EFFICACY OF THORACIC PARAVERTEBRAL BLOCK ANESTHESIA IN BREAST AUGMENTATION SURGERY. Sarh Alaeed , Rahaf Mandura , Maan Kattan , Basim Alsaywid and Wesam Abuznadah. General physician, King Salman Armed Forces Hospital, Tabuk, Saudi Arabia. Ophthalmology teaching assistant, King Abdulaziz university, PGY 2 Saudi Board of Ophthalmology, Jeddah, Saudi Arabia. Anesthesia department chairman, Consultant anesthesiologist and pain physician, King Abdulaziz Medical City, Jeddah, Saudi Arabia. Pediatric Urologist and Epidemiologist, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia. Assistant professor of vascular Surgery, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Jeddah, Saudi Arabia.

Blocking ion channels induced by antifungal lipopeptide syringomycin E with amide-linked local anesthetics

The effects of the amide-linked (lidocaine (LDC), mepivacaine (MPV), prilocaine (PLC)) and ester-bound local anesthetics (benzocaine (BZC), procaine (PRC), and tetracaine (TTC)) on the pore-forming activity of the antifungal lipopeptide syringomycin E (SRE) in lipid bilayers were studied. Independently on electrolyte concentration in the membrane bathing solution the observed changes in conductance of SRE channels agreed with the altered membrane dipole potential under the action of ester-bound local anesthetics. Effects of aminoamides in diluted and concentrated solutions were completely different. At 0.1 M KCl (pH 7.4) the effects of amide-linked anesthetics were in accordance with changes in the membrane surface potential, while at 2 M KCl aminoamides blocked ion passage through the SRE channels, leading to sharp reductions in pore conductance at negative voltages and 100-fold decreases in the channel lifetimes. The effects were not practically influenced by the membrane lipid composition. The interaction cooperativity implied the existence of specific binding sites for amide-bound anesthetics in SRE channels.

A state-of-the-art approach for facile and reliable determination of benzocaine in pharmaceuticals and biological samples based on the use of miniaturized boron-doped diamond electrochemical sensor

For the first time, the miniaturized thick-film boron-doped diamond electrode was applied as progressive electrochemical sensor for simple, facile and reliable quantification of local anesthetic agent, benzocaine (BZC). Cyclic voltammetric measurements revealed that the electrode reaction of this analyte was manifested by one irreversible and diffusion-driven oxidation peak at +1.0 V in Britton-Robinson buffer at pH 4.0. Pulse voltammetric techniques with the suitably chosen values of operating parameters were used for the construction of calibration curves for BZC determination with the essential analytical characteristics as follows: the linear concentration range of 0.1–400 μM and 0.4–200 μM, the limit of detection of 80 nM and 100 nM for differential pulse voltammetry (DPV) and square-wave voltammetry (SWV), respectively. The excellent repeatability with the relative standard deviation below 5% was reached for both pulse voltammetric techniques. The developed protocols were applied to analysis of the commercial pharmaceuticals with the recoveries ranging from 97.4 to 104.5% and from 97.0 to 102.7% for DPV and SWV procedures as well as model human urine samples with recoveries from 96.0 to 104.0% and from 98.5 to 100.8%. This platform based on biocompatible, portable and easy-to-operate electrochemical sensor could encourage the viability of the proposed state-of-the-art approach for field applications, such as quality control of pharmaceuticals and monitoring of BZC in biological samples.

Synthesis of polyamide 6 with aramid units by combination of anionic ring-opening and condensation reactions

Polyamides with different percentages of aromatic/aliphatic units and molar masses were synthesized in a one-step bulk copolymerization of ε-caprolactam and ethyl 4-aminobenzoate at 140 °C keeping the same experimental conditions basically used for the synthesis of polyamides by anionic ring opening polymerization (AROP). Copolyamides were characterized by NMR spectroscopy, size exclusion chromatography and thermo-mechanical analysis (DSC, TGA and DMA). This methodology, combining simultaneous anionic ring-opening and condensation reactions, affords a new route to introduce aromatic amides into an aliphatic polyamide backbone and tune its properties. Modified polyamides 6 (PA6) obtained from ε-caprolactam by an activated monomer mechanism and containing up to 17% mol of aromatic moiety were prepared. The new materials exhibited in particular high thermal stability and high glass transition temperature up to 79 °C.

Characterization and cytotoxicity of a benzocaine inclusion complex

Benzocaine (BZC), is a local anesthetic widely used in topical formulations as well as in throat pastilles. A disadvantage is that the compound presents low aqueous solubility. The present work describes the preparation and characterization of an inclusion complex between BZC and β-cyclodextrin (β-CD), followed by cytotoxicity assays. The association constant (Ka) was calculated using solubility isotherms, at different temperatures, and an HPLC procedure, at room temperature, employing a reverse phase C18 column, with a mobile phase consisting of water/acetonitrile. Ka obtained with solubility isotherms at temperatures of 25, 35, and 45 °C were 229.8, 317.1, and 520.3 M−1, respectively. Employing HPLC, Ka was 38.0 M−1. The difference in the Ka value could be explained because HPLC analyses were conducted using organic solvent, which affected the host–guest interaction. Moreover, the continuous flow could have altered the degree of association of the drug with β-CD. The BZC/CD inclusion complex was characterized using infrared spectroscopy, thermogravimetry, and X-ray diffraction. Analysis showed a good agreement with literature, suggesting that the complex was established. Cytotoxicity assays using fibroblast V79 cells showed that BZC/CD formulation was not cytotoxic, demonstrating its potential to reduce the toxicity of the anesthetic. The assays demonstrated an effective interaction between BZC and CD, and that the inclusion complex was less toxic to V79 cells than the plain BZC, turning it a good alternative to decrease its toxicity when administered to patients.

Structure-function insights into chikungunya virus capsid protein: Small molecules targeting capsid hydrophobic pocket

The crystal structure of chikungunya (CHIKV) virus capsid protease domain has been determined at 2.2Å. Structure reveals a chymotrypsin-like protease fold with a conserved hydrophobic pocket in CHIKV capsid protein (CP) for interaction with the cytoplasmic tail of E2 (cdE2) similar to the capsid protein of other alphaviruses. Molecular contacts between CP-cdE2 were determined by fitting structures of CHIKV CP and cdE2 into the cryo-EM map of Venezuelan equine encephalitis virus (VEEV). Binding of (S)-(+)-Mandelic acid (MDA) and Ethyl 3-aminobenzoate (EAB) to the hydrophobic pocket of CP was evaluated by molecular docking. Surface plasmon resonance (SPR) and fluorescence spectroscopy experiments confirmed MDA and EAB binding to the CP. The binding constants (KD) obtained from SPR for MDA and EAB were 1.2 × 10−3 M and 0.2 × 10−9 M, respectively. This study adds to the understanding of chikungunya virus structural proteins and may serve as the basis for antiviral development against chikungunya disease.

Photoinitiator and anesthetic incorporation into mesoporous silica

The sol–gel methodology affords mesoporous silica with controlled pore size. The resulting materials can be used to incorporate, immobilize, or encapsulate several molecules for further application as drug delivery systems, antibacterials, and photonic devices, just to mention a few examples. Dental resins employed in tooth repair consist of an organic matrix, a charged inorganic component, and union agents; a photoinitiator triggers resin polymerization. In this work, we incorporated the photoinitiator camphorquinone or the anesthetic ethyl 4-aminobenzoate into mesoporous silica. Characterization of the materials by infrared and electronic spectroscopy, thermal analysis, X-ray diffraction, and specific surface area confirmed the presence of the photoinitiator or the anesthetic in the silica matrix. Kinetic and equilibrium assays as well as absorption studies showed that the mesoporous silica obtained here can be applied as a drug delivery system.

Blood Clinical Biochemistries and Packed Cell Volumes for the Mexican Axolotl (Ambystoma mexicanum)

Abstract Mexican axolotls (Ambystoma mexicanum) are used as research animals in a variety of fields, and are also kept as pets. However, there are limited clinical pathology references available for Mexican axolotls that can be used to interpret cases with clinical disease. To establish plasma biochemical and packed cell volume reference intervals, we collected blood samples from 43 clinically healthy Mexican axolotls (mean body weight, 59.6 ± 17.5 g; total length, 21.1 ± 1.8 cm) under anesthesia with a 0.2% ethyl 3-aminobenzoate methanesulfonate solution. Plasma biochemical tests were performed with the use of two types of automated biochemical analyzers, and packed cell volume was measured simultaneously. Bland–Altman analysis was used to measure agreement between the analyzers. Reference intervals for packed cell volume and plasma biochemical values obtained from both analyzers were established for the Mexican axolotl. The results revealed systematic biases in values derived from both analyzers. This s...

EFFECT OF NASAL HIGH FLOW SYSTEM ON OXYGENATION DURING SEDATION UNDER SPINAL ANESTHESIA IN ELDERLY PATIENTS

RespirologyVolume 22, Issue S3 p. 227-227 APSR Poster Abstracts EFFECT OF NASAL HIGH FLOW SYSTEM ON OXYGENATION DURING SEDATION UNDER SPINAL ANESTHESIA IN ELDERLY PATIENTS First published: 23 November 2017 https://doi.org/10.1111/resp.13207_365Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 227-227 RelatedInformation

Optimizing Hydrophobic Groups in Amphiphiles to Induce Gold Nanoparticle Complex Vesicles for Stability Regulation.

Polymeric graft polyphosphazene containing 4-aminobenzoic acid diethylaminoethyl ester (DEAAB) as hydrophobic side groups was rationally designed and named PDEP. PDEP can self-assemble into a nanovesicle in water. More importantly, when compared with the amphiphile poly[(methoxy-poly(ethylene glycol))(ethyl p-aminobenzoate)]phosphazene (PEP) copolymer containing benzene rings and the amphiphile poly[(methoxy-poly(ethylene glycol)(N,N-diisopropylethylenediamine)]phosphazene (PDP) copolymer containing tertiary amino groups, the coexistence of benzene and tertiary amino groups in PDEP enabled it to effectively load water-soluble small-molecule doxorubicin hydrochloride (DOX·HCl) into the vesicle and efficiently induce in situ transformation of gold tetrachloroaurate (HAuCl4) to gold nanoparticles (AuNPs) as both a reductant and a stabilizer. By optimizing the reduction conditions, such as the temperature, reaction time, and hydrophobic group in polymer/HAuCl4 molar ratio, the AuNP complex PDEP vesicles significantly inhibited the DOX·HCl burst release at pH 7.4 while displaying a fast release responsive to pH 5.5.

Quantum chemical investigations on hydrogen bonding interactions established in the inclusion complex β-cyclodextrin/benzocaine through the DFT, AIM and NBO approaches

Structure and stability of an inclusion complex formed by Benzocaine (BZC) and β-cyclodextrin (β-CD) were investigated computationally using different levels of theory. The conformational research based on PM6 method allowed reach two minimum-energy structures: model A and model B. The lowest conformers have been exposed to fully geometry optimization employing four DFT functionals: B3LYP, CAM-B3LYP, M05-2X and M06-2X. The performed DFT calculations have identified the model B, in which the amino group is located at the primary face of β-CD, as the most stable complex by an amount up to −40 kcal/mol. Further, the greater stabilization of model B in respect to model A, has been ascertained through AIM and NBO analyses which clarified the main hydrogen bonds HBs interactions governing the reactivity of BZC inside the hydrophobic cavity of β-CD. Finally, the estimated isotropic 1H nuclear magnetic shielding constants generated from the gauge-including-atomic-orbital calculation have been analyzed and then compared with the available experimental data.

Solubility and preferential solvation of benzocaine in {methanol (1) + water (2)} mixtures at 298.15 K

ABSTRACTThe equilibrium solubility of benzocaine (BZC) in several {methanol (1) + water (2)} mixtures at 298.15 K was determined. Solubility values are expressed in mole fraction and molarity and were calculated with the Jouyban–Acree model. Preferential solvation parameters of BZC by methanol (δx1,3) were derived from their thermodynamic solution properties using the inverse Kirkwood–Buff integrals method. δx1,3 values are negative in water-rich mixtures (0.00 < x1 < 0.32) but positive in the other mixtures (0.32 < x1 < 1.00). To explain the preferential solvation by water in the former case, it is conjecturable that the hydrophobic hydration around non-polar groups of BZC plays a relevant role in the solvation. Moreover, the higher solvation by methanol in mixtures of similar cosolvent compositions and methanol-rich mixtures could be explained in terms of the higher basic behaviour of methanol regarding water.

Synthesis and in vitro degradation studies of substituted poly(organophosphazenes) for drug delivery applications

The synthesis, characterization and in vitro degradation studies of controlled molecular weight degradable poly(organophosphazenes) bearing various hydrophilic and hydrophobic side group is reported. The polymerization was carried out by thermal polymerization of cyclic trimer hexachlorocyclotriphosphazene at 260 ± 5 °C for 4–5 h to yield poly(dichlorophosphazene). This polymer backbone was suitably substituted with sodium or potassium salts of alcoholic or phenolic compounds and ethyl 4-aminobenzoate to obtain substituted poly(organophosphazenes). The characterization of polymers was carried out by IR, 1H NMR and 31P NMR. The molecular weights of these novel polyphosphazenes were determined using size exclusion chromatography with a Waters 515 HPLC Pump and a Waters 2414 refractive index detector. The degradation behavior was studied by 200 mg pellets of polymers in phosphate buffers pH 5.5, 6.8 and 7.4 at 37 °C. These polymers exhibited hydrolytic degradability, which can afford applications to a variety of drug delivery systems. This study shows that poly(organo)phosphazenes could be a potential novel class of biodegradable polymeric carriers for targeted drug delivery.

Titanium nanoparticles (TiO2)/graphene oxide nanosheets (GO): an electrochemical sensing platform for the sensitive and simultaneous determination of benzocaine in the presence of antipyrine.

An effective electrochemical sensing platform for the simultaneous determination of benzocaine (BEN) and antipyrine (ANT) based upon titanium dioxide nanoparticle (TiO2)/graphene oxide nanosheet (GO) bulk modified carbon paste electrodes (TiO2-GO/CPE) is reported. The TiO2-GO/CPE electrochemical sensing platform is found to exhibit linear ranges from 1.0 × 10-6 to 1.0 × 10-4 M and 1.2 × 10-8 to 8.0 × 10-5 M for BEN and ANT, respectively. The TiO2-GO/CPE sensor is explored towards the analysis of BEN and ANT in oral fluid (saliva) and pharmaceutical products. The synergy between the graphene oxide nanosheets and titanium dioxide nanoparticles results in a dramatic enhancement in the sensitivity of the sensor through a combination of increased surface area and improved electron transfer kinetics compared to other electrode alternatives. The fabricated TiO2-GO/CPE exhibits high sensitivity and good stability towards the sensing of BEN and ANT and has the potential to be utilised as a clinical assay and QA in pharmaceutical products.

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English

Study on growth, structural, optical, thermal and mechanical properties of organic single crystal ethyl p-amino benzoate (EPAB) grown using vertical Bridgman technique

Ethyl p-aminobenzoate (EPAB) single crystal was grown using vertical Bridgman technique (VBT). The crystal system of grown crystal was identified, and lattice parameters have been measured from the powder X-ray diffraction (PXRD). The optical transparency of EPAB single crystal was 55%, and the cut-off wavelength was found to be 337nm. The thermal stability of EPAB single crystal was analyzed by thermogravimetric analysis. Etching studie were carried out for the grown crystal using different solvents, and etch pit density (EPD) was calculated and compared. Vickers microhardness (Hv) measurements revealed that EPAB belongs to the category of soft material. The dielectric studies reveal that the dielectric constant and dielectric loss of grown crystal decreases with increasing frequency for various temperatures. The third-order nonlinear optical property of EPAB was investigated and compared with other organic crystals. The evaluation of third-order optical properties such as nonlinear refractive index (n2), nonlinear absorption (β) and third-order nonlinear susceptibility (χ3) have found to be in the range of 10−11m2/W, 10−4m/W and 10−5esu respectively. The Laser damage threshold energy of EPAB was measured using Nd: YAG laser. The blue emission of the grown crystal was identified by photoluminescence (PL) spectra measurements. The second harmonic generation (SHG) for the grown EPAB crystal was confirmed by Kurtz powder technique.

Simple spectrophotometric methods for the simultaneous determination of antipyrine and benzocaine

Antipyrine and benzocaine are formulated together for the treatment of ear inflammation and to relieve pain. Four spectrophotometric methods were developed for the simultaneous determination of antipyrine (AN) and benzocaine (BE) in their combined dosage form. Method A depends on applying dual wavelength method where antipyrine was determined by measuring the absorbance at 254.1 and 309.1nm (corresponding to zero difference of benzocaine), while the absorbance difference at 230.1 and 263.5nm (corresponding to zero difference of antipyrine) was selected for benzocaine determination in the laboratory prepared spectrum. Method B depends on measuring the peak amplitude of first derivative at 305nm for calculating benzocaine concentration then the total concentration of both drugs was determined using isoabsorptive point at 257.4nm (antipyrine concentration was then calculated by subtraction). Method C is based on measuring the peak difference of the ratio spectra at Δp (239.1–285nm) and Δp (301.4–250nm) for the determination of antipyrine and benzocaine, respectively. Method D depends on measuring peak to peak amplitude of the first derivative of ratio spectra at (234.5+244.2nm) and peak amplitude at 295.5nm for the determination of antipyrine and benzocaine, respectively. The proposed methods were validated and applied for the analysis of antipyrine and benzocaine in their laboratory prepared mixtures and pharmaceutical formulation. Statistical comparison between the results of the proposed methods and those of the reported methods showed no significant difference.

Solubility of Ethyl p-Aminobenzoate in Six Alcohols within (283.15 to 327.15) K

The solubility of ethyl p-aminobenzoate (EPAB) was measured in six different alcohols (methanol, ethanol, n-propanol, n-butanol, isobutyl alcohol, isoamyl alcohol) within (283.15 to 327.15) K by the last solid disappearance method. The solubility increases with increasing temperature. The decreasing order satisfies the following sequence: methanol > ethanol > n-propanol > n-butanol > isoamyl alcohol > isobutyl alcohol. Four models, including modified Apelblat equation, λh model, NRTL model, and Wilson model, were used to correlate the experimental data of EPAB. It is found that the modified Apelblat equation, NRTL model, and Wilson model were suitable to correlate the solubility of EPAB in the selected solvents with an overall RAD less than 2%. In addition, the changes of thermodynamic properties of solution [standard molar enthalpy (ΔdisHo), standard molar entropy (ΔdisSo), and standard molar Gibbs energy (ΔdisGo)] were obtained. The results indicate that the dissolution process of EPAB in these alcohols...

Preparation and evaluation of novel microemulsion-based hydrogels for dermal delivery of benzocaine

The purpose of the current research was to prepare and evaluate the potential use of microemulsion-based hydrogel (MBH) formulations for dermal delivery of benzocaine (BZN). The pseudoternary-phase diagrams were constructed for various microemulsions composed of isopropyl myristate (IPM) as oil phase, Span 20, Tween 20, Tween 80, cremophor EL and cremophor RH40 as surfactants, ethanol as cosurfactant and distilled water as aqueous phase. Finally, concentration of BZN in microemulsions was 2% (w/w). The physicochemical properties, such as conductivity, viscosity, pH, droplet size, polydispersity index and zeta potential of microemulsions, were measured. Carbopol 940 was used to convert BZN-loaded microemulsions into gel form without affecting their structure. Furthermore, excised rat abdominal skin was used to compare permeation and penetration properties of BZN loaded M3 and M3BHs with BZN solution. According to ex vivo study results, BZN-loaded M3BH1 showed highest flux values and high release rate values, and furthermore, this gel formulation had low surfactant content. Finally, in order to learn the localization of formulations within the dermal penetration, formulations and BZN solution were labeled with red oil O and subjected to fluorescence observation. In conclusion, BZN-loaded MBHs could be offered as a promising strategy for dermal drug delivery.