Promethazine Research Articles

Phase separation and aggregation phenomena of TX-100 and promethazine hydrochloride mixture: Influences of monohydroxy organic compounds

Clouding nature and thermodynamic characteristics of surfactant-drug systems are novel approaches to chemists, industrialists, and researchers due to the enormous applications of the such mixture in pharmaceutical as well as technological sectors. In this study, the phase separation, assembly formation, and thermodynamic properties of triton X-100 (TX-100) + promethazine hydrochloride (PMH) drug mixed system were investigated by means of cloud point (CP) measurement and UV–visible spectroscopic techniques. The influences of the monohydroxy alcohols (ethanol (EtOH), 1-propanol (1-PrOH), 2-propanol (2-PrOH), along with 2-methyl-1-propanol (iso-BuOH) on the clouding development of TX-100 + drug mixed system have also been demonstrated. At lower concentrations of aqueous alcoholic media, the variation of CP with the enhancement of concentrations of alcohol were observed and increased CP values follow the trend: CPH2O+2-PrOH>CPH2O+EtOH>CPH2O+iso-BuOH>CPH2O+1-PrOH. The critical micelle concentration (CMC) of TX-100 + PMH mixture was found to be experienced an augmentation with the boost of the temperature. The obtained free energy values revealed the non-spontaneity of clouding and spontaneous aggregation of TX-100 + PMH mixture. The non-spontaneity of clouding of TX-100 + PMH mixture reduces with enhancement of concentrations of alcohols. The ΔHc0 and ΔSc0 values were found to be positive in almost all cases except at higher concentration of aq. 2-PrOH and iso-BuOH which disclosed the existence of hydrophobic as well as electrostatic interactions. The micellization of TX-100 + PMH mixed system in an aqueous medium was also accompanied by the hydrophobic interaction. The entropy-enthalpy compensation parameters of the clouding and micellization phenomenon were also elucidated through appropriate explanations.

Development of the New Sensor Based on Functionalized Carbon Nanomaterials for Promethazine Hydrochloride Determination

Promethazine hydrochloride (PM) is a widely used drug so its determination is important. Solid-contact potentiometric sensors could be an appropriate solution for that purpose due to their analytical properties. The aim of this research was to develop solid-contact sensor for potentiometric determination of PM. It had a liquid membrane containing hybrid sensing material based on functionalized carbon nanomaterials and PM ions. The membrane composition for the new PM sensor was optimized by varying different membrane plasticizers and the content of the sensing material. The plasticizer was selected based on calculations of Hansen solubility parameters (HSP) and experimental data. The best analytical performances were obtained using a sensor with 2-nitrophenyl phenyl ether (NPPE) as the plasticizer and 4% of the sensing material. It had a Nernstian slope (59.4 mV/decade of activity), a wide working range (6.2 × 10-7 M-5.0 × 10-3 M), a low limit of detection (1.5 × 10-7 M), fast response time (6 s), low signal drift (-1.2 mV/h), and good selectivity. The working pH range of the sensor was between 2 and 7. The new PM sensor was successfully used for accurate PM determination in a pure aqueous PM solution and pharmaceutical products. For that purpose, the Gran method and potentiometric titration were used.

Promethazine inhibits efflux, enhances antifungal susceptibility and disrupts biofilm structure and functioning in Trichosporon

Trichosporon spp. are emerging opportunistic fungi associated with invasive infections, especially in patients with haematological malignancies. The present study investigated the in vitro inhibition of efflux pumps by promethazine (PMZ) as a strategy to control T. asahii and T. inkin. Planktonic cells were evaluated for antifungal susceptibility to PMZ, as well as inhibition of efflux. The effect of PMZ was also studied in Trichosporon biofilms. PMZ inhibited T. asahii and T. inkin planktonic cells at concentrations ranging from 32 to 256 μg ml–1. Subinhibitory concentrations of PMZ inhibited efflux activity in Trichosporon. Biofilms were completely eradicated by PMZ. PMZ potentiated the action of antifungals, affected the morphology, changed the amount of carbohydrates and proteins and reduced the amount of persister cells inside biofilms. The results showed indirect evidences of the occurrence of efflux pumps in Trichosporon and opens a perspective for the use of this target in the control of trichosporonosis.

Micellization behavior of promethazine hydrochloride and dimethyldodecylethylammonium bromide mixture in distinctive media: A multi-technique study

Herein, we studied the impact of cationic surfactant dimethyldodecylethylammonium bromide (DMDEABr) on the micellization of promethazine hydrochloride (PMH) through different methods: surface tensions, UV, and FT-IR. DMDEABr surfactant behaves synergistically with PMH in all media (H2O, 50 mmol.kg−1 NaCl, and 200 mmol.kg−1 fructose). The accomplished outcomes of critical micelles concentration (cmc) of PMH + DMDEABr from the tensiometry method observed significant deviation from their comparable ideal value (cmcid) which unveiled the nonideal behavior of PMH + DMDEABr mixture. When fructose is added to solutions of PMH, DMDEABr, and PMH + DMDEABr, cmc increases as well as decreases depending on the concentration of fructose. Here, the concentration of fructose employed decreases cmc value, whereas added NaCl decreases cmc value more. DMDEABr is found to have a higher micellar composition in mixed micelles than PMH except at the lowest employed mole fraction (α1) of DMDEABr. Interaction parameters (mixed micellar/mixed interface) demonstrated the attractive/synergism amongst PMH and DMDEABr. Numerous thermodynamic parameter evaluations showed that mixed systems are both spontaneous and stable. PMH's absorption intensity increased due to DMDEABr's interaction with PMH as observed by UV–visible spectra. In addition to identifying peak shifting in spectra of PMH (pure component), FT-IR analyses confirmed that PMH and DMDEABr were interacting with each other. Drug delivery across membranes can be greatly enhanced when mixed micelles form since they increase solubility and permeability.

Taste Masking of Promethazine Hydrochloride Using l-Arginine Polyamide-Based Nanocapsules.

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of -31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.

Mannosylated Gold Nanoclusters Incorporated with a Repurposed Antihistamine Drug Promethazine for Antibacterial and Antibiofilm Applications.

Drug repurposing presents a workable strategy in tackling antibiotic resistance. Many known drugs have been repurposed for their applications against different targets. Antihistamines that are usually used to treat allergy symptoms can be combined with nanoscale materials to enhance their efficiency. Herein, we explored the antimicrobial properties of a common antihistamine drug, promethazine, in Gram-positive and Gram-negative bacteria. Being positively charged, promethazine was easily incorporated into the mannose-conjugated bovine serum albumin-stabilized promethazine hydrochloride gold nanoclusters. Capping with d-mannose helped in targeting the bacteria by inhibiting their adhesive appendage called pili. Following their uptake, drugs released inside the bacteria caused reactive oxygen species production and membrane permeability alteration, ultimately resulting in bacterial inhibition. Additionally, they were also explored for biofilm eradication. As observed through staining assays, the number of dead cells increased with increasing concentration of drug-loaded gold nanoclusters in the biofilm mass. Therefore, the as-synthesized mannosylated gold nanoclusters incorporated with promethazine were analyzed for potential antibacterial and antibiofilm applications.

The Potential of Phenothiazines against Endodontic Pathogens: A Focus on Enterococcus-Candida Dual-Species Biofilm.

Persistent apical periodontitis occurs when the endodontic treatment fails to eradicate the intraradicular infection, and is mainly caused by Gram-positive bacteria and yeasts, such as Enterococcus faecalis and Candida albicans, respectively. Phenothiazines have been described as potential antimicrobials against bacteria and fungi. This study aimed to investigate the antimicrobial potential of promethazine (PMZ) and chlorpromazine (CPZ) against E. faecalis and C. albicans dual-species biofilms. The susceptibility of planktonic cells to phenothiazines, chlorhexidine (CHX) and sodium hypochlorite (NaOCl) was initially analyzed by broth microdilution. Interaction between phenothiazines and CHX was examined by chequerboard assay. The effect of NaOCl, PMZ, CPZ, CHX, PMZ + CHX, and CPZ + CHX on biofilms was investigated by susceptibility assays, biochemical and morphological analyses. Results were evaluated through one-way ANOVA and Tukey's multiple comparison post-test. PMZ, alone or in combination with irrigants, was the most efficient phenothiazine, capable of reducing cell counts, biomass, biovolume, carbohydrate and protein contents of dual-species biofilms. Neither PMZ nor CPZ increased the antimicrobial activity of CHX. Further investigations of the properties of phenothiazines should be performed to encourage their use in endodontic clinical practice.

Acute Toxicity of a Marine Emerging Pollutant (Promethazine Hydrochloride) on Artemia sp.

Recently, there has been a worrying increase in the pollution of the aquatic ecosystem caused by emerging contaminants (ECs) detected in wastewater effluent discharges. Although traces of ECs in waters have been found in low concentrations, it leads to negative effects for nontarget organisms. Antihistamines are a class of drugs largely used, whose metabolites are widespread in the aquatic ecosystem. The aim of the study was to evaluate the short-term effects of promethazine hydrochloride on nauplii of Artemia sp. A high percentage of mortality and morphological alterations were found. The results suggest a possible correlation between exposure to antihistamine and an acceleration of larval development.

Spectrophotometric Determination of Promethazine Hydrochloride by In (III)

A simple, rapid and sensitive spectrophotometirc method for the determination of trace amounts of promethazine hydrochloride in the aqueous solution is described. The method is based on the complexation of promethazine hydrochloride with In (III) in the presence of sodium hydroxide to form an soluble product with maximum absorption at 304nm. Beer’s law is obeyed over the concentration range of (2-20μg/ml) with molar absorptivity of (1.92× 103 L.mol-1.cm-1). The optimum conditions for all development are described and the proposed method has been successfully applied for the determination of promethazine hydrochloride in bulk drug.

Promethazine hydrochloride reduces children's agitation during ocular examination for trauma.

Examination and intervention are always the causes of agitation, anxiety, and fear in children's lives. This study aimed to investigate the effectiveness of promethazine hydrochloride in reducing children's agitation during the ocular examination for trauma. In this interventional-clinical trial study, a total of 62 children referred to Al-Zahra Ophthalmology Hospital in Zahedan, Iran, were evaluated in two matched groups (case (n = 31) and control (n = 31)) for an initial examination of ocular trauma. Finally, the intervention was performed (giving placebo or promethazine hydrochloride cough syrup 20 minutes before the initial ocular examination at 0.5 mg/kg), and the demographic information form and researcher-made questionnaire modeled on the Cohen-Mansfield Agitation Inventory (CMAI) were completed. The obtained results revealed that the mean scores of physical/aggressive behaviors (p ˂ 0.001), physical/nonaggressive behaviors (p = 0.013), verbal/aggressive behaviors (p ˂ 0.001), and hiding behaviors (p ˂ 0.001) were significantly lower in the promethazine hydrochloride-receiving group than the placebo group. These findings demonstrated that promethazine hydrochloride cough syrup facilitated the examination among the pediatric patients who suffered from traumatic ocular injuries. However, further studies in this field need to be carried out through randomized controlled trials.

Phase separation and conductivity studies on the interaction of promethazine hydrochloride drug with cationic and nonionic surfactants: influences of electrolytes and temperature

• Phase separation of TX-100 + promethazine hydrochloride (PMH) was studied in presence of salts. • Assembly of TTAB + PMH drug has been investigated at different temperatures. • CP of TX-100 + PMH mixture in salts media, follow the order: K 3 PO 4 < K 2 SO 4 < KCl. • Thermodynamic parameters (phase separation/aggregation processes) are computed. • Phase separation/aggregation of system was found nonspontaneous/spontaneous. Here, the phase separation of the mixture of triton X-100 (TX-100) and promethazine hydrochloride (PMH), as well as the assembly of the mixture of tetradecyltrimethylammonium bromide (TTAB) and PMH drug, have been investigated. The cloud points (CP) of TX-100 in the manifestation of PMH/PMH + salts (KCl, K 2 SO 4 , and K 3 PO 4 ) were determined, while the CP values were found to vary with the contents of PMH and salts. The CP of TX-100 + PMH mixture, at a particular PMH concentration in salts media, follow the order: K 3 PO 4 < K 2 SO 4 < KCl. The micellar parameters were determined from the conductivity versus [TTAB] plots. The conductivities and micellar parameters of the TTAB + PMH mixture in salts media were found to vary through the fluctuation of temperature. The thermodynamic variables (free energy (Δ G 0 ), enthalpy (Δ H 0 ), and entropy (Δ S 0 ) changes) for the phase separation and aggregation phenomena of the mixture of surfactant + drug mixture have been computed in the current studies. The phase separation of TX-100 + PMH mixtures was nonspontaneous (+Δ G 0 c values) and assembly of the TTAB + PMH mixture was spontaneous (–Δ G 0 m values). The other thermodynamic variables, in addition to enthalpy–entropy compensation parameters, have also been evaluated and illustrated with proper explanation.

Polyethyleneimine stabilized silver nanoparticles as an efficient and selective colorimetric assay for promethazine

Development of simple, facile, and on-spot colorimetric assays for drugs and pesticides based on metal nanoparticles is an emerging field of modern scientific research. Herein, a branched polyethyleneimine (PEI) is used to stabilize silver nanoparticles (AgNPs) through a simple one-pot, two-phase protocol. As the primary goal of the research, the synthesized PEI-AgNPs are employed for an efficient and selective quantitative detection of promethazine (PRO). The typical yellow color of PEI-AgNPs changed to orangish-brown as soon as PRO is added which is further endorsed by an increase in the intensity of the SPR band. The electrostatic forces are responsible for the steric stabilization of silver ions in the micro-domains of the PEI. PRO addition in PEI-AgNPs decreased the average hydrodynamic size and increased apparent positive charge of AgNPs. These changes might be attributed to the presence of the sulfur group in PRO. The limit of detection, the limit of quantification, and the dynamic range of detection of PRO through PEI-AgNPs are found to be 0.003 μM, 0.1 μM, and 0.1–200 μM, respectively. Moreover, PEI-AgNPs allowed reliable, efficient, selective, and quick quantitative detection of PRO in environmental, biological, and commercial drug samples in the presence of other interfering drugs and metal salts. The proposed PRO sensor renders an excellent platform for its quick and on-spot detection without requiring a well-equipped lab setup. Up to the best of our knowledge, the proposed PRO sensor is the first of its kind (colorimetric) in the list of proposed instrumental methods for determination of PRO. The quantitation of PRO as obtained by proposed sensor is compared with UV–Vis spectroscopy and UPLC. Finally, excellent performance of PEI-AgNPs based sensor for biological, environmental, and commercial samples is demonstrated in comparison to UV–Vis spectroscopy and UPLC.

Fabricating BiOCl/BiVO4 nanosheets wrapped in a graphene oxide heterojunction composite for detection of an antihistamine in biological samples

Antibiotics are essential medications for human and animal health, as they are used to battle urinary infections and bacterial diseases. Therefore, the rapid determination of antibiotic drugs in biological samples is necessary to address the current clinical challenge. Here, we developed a heterojunction ternary composite of BiOCl/BiVO4 nanosheets enriched with graphene oxide (BiOCl/BiVO4@GO) for accurate and minimal-level detection of an antihistamine (promethazine hydrochloride, PMZ) in urine samples. The BiOCl/BiVO4 nanosheets were prepared by a wet chemical approach using a deep eutectic green solvent. The spectroscopic and analytical methods verified the formation and interaction of the BiOCl/BiVO4@GO composite. Our results showed that the thoroughly exfoliated BiOCl/BiVO4@GO composite retained good electrical conductivity and fast charge transfer toward the electrode–electrolyte interface in neutral aqueous media. In addition, the experimental conditions were accurately optimized, and the BiOCl/BiVO4@GO composite showed excellent electrocatalytic activity toward the oxidation of PMZ. Indeed, the BiOCl/BiVO4@GO composite demonstrated a good linear response range (0.01–124.7 μM) and a detection level of 3.3 nM with a sensitivity of 1.586 μA μM−1 cm−2. In addition, the BiOCl/BiVO4@GO composite had excellent storage stability, good reproducibility, and reliable selectivity. Finally, the BiOCl/BiVO4@GO displayed a desirable recovery level of PMZ in urine samples for real-time monitoring.

A comparative study of the effect of phenothiazine derivatives and their S-oxides on cholinesterase investigated by a new kinetic spectrophotometric method

Aim. To develop a new kinetic spectrophotometric method for determining acetylcholinesterase (AChE) inhibitors – phenothiazine antipsychotic drugs (PhT) and their sulfoxide metabolites (S-oxides) without adding an exogenous catalyst to obtain a chromogenic agent.Materials and methods. The bases of S-oxides of promethazine (PMZ), chlorpromazine (CPM) and thioridazine (THZ) were obtained by oxidizing the corresponding PhT hydrochlorides with diperoxyadipic acid. The structure of the S-oxides of the corresponding PhT synthesized was proven by melting points, spectral characteristics (1H NMR and IR methods) and oscillopolarography results. 1H NMR spectra were recorded on a Varian XL-200 spectrometer. IR spectra were recorded within the range of 4000-400 cm–1 on a SPECORD M-80 spectrometer (Zeiss, Jena, Germany). To register polarograms, a “PO 03 CLA” oscillopolarograph with a three-electrode cell was used. The purity of S-oxides was determined by the high-performance liquid chromatography method on a Zorbax SB, C-18 (250 × 4.6) mm column. Measurements of absorbance of solutions were performed in a 1 cm cuvette on an Evolution 60S UV-Visible Thermo-Scientific Spectrophotometer (USA) (λ = 358 nm).Results and discussion. Acetylcholine (ACh) was found to mimic the activity of peroxidase; based on it, a spectrophotometric system containing ACh–H2O2–p-Ph for a sensitive and selective assessment of the AChE activity and determination of its inhibitors was developed. According to the plots of inhibition efficiency vs inhibitors concentration, the inhibiting ability of chlorpromazine, promethazine and thioridazine and their S-oxides was determined. The IC50 values of CPM, PMZ and THZ and their metabolites in relation to the AChE activity were estimated as 11 ng mL−1 (CPM) and 1.8 ng mL−1 (CPM S-oxide), 17 ng mL−1 (PMZ) and 2.5 ng mL−1 (PMZ S-oxide) and 27 ng mL−1 (THZ 2S,5S-dioxide). The results obtained indicate that S-oxides of the corresponding PhT are selective and potent inhibitors of AChE. The values of the inhibition efficiency obtained for S-oxides of PhT derivatives were an order of magnitude lower than those of the corresponding PhT derivatives.Conclusions. The spectrophotometric method proposed without the addition of other exogenous catalysts holds promise for the on-site determination of PhT antipsychotics and can be additionally used for sensory applications in areas related to environmental protection and food safety, as well as in the chemical-toxicological analysis.

The electrochemical evaluation of antipsychotic drug (promethazine) in biological and environmental samples through samarium cobalt oxide nanoparticles

In this work, we developed a perovskite structured samarium cobalt oxide nanoparticles (SmCoO3 NPs) with the aid of the co-precipitation method. The rare earth metal (Sm) and cobalt oxide combined to form a perovskite lattice structure. One-pot route synthesized SmCoO3 NPs were scrutinized successfully through various physicochemical techniques. Concerning its effective thermal stability and electrical properties, the synthesized SmCoO3 NPs have been effectively implemented in the electrochemical evaluation of promethazine hydrochloride (PHY) using cyclic voltammetry. The electrochemical detection of PHY was performed through SmCoO3 NPs-modified glassy carbon electrode (GCE) and unmodified GCE. The electron transfer kinetics, effect of scan rate, the influence of pH, electroactive surface area, selectivity, and sensitivity have been studied. The electron charge transfer rate (Rct) and electrolyte resistance (Rs) were calculated to be 105.59 (Ω) and 150 (Ω) in the ferricyanide probe, indicating great facilitation of the electron transfer between PHY and SmCoO3 NPs deposited on the electrode surface. Further, the optimized SmCoO3-modified GCE exemplifies excellent selectivity, storage stability, reproducibility, repeatability, detection limit (5 nM), sensitivity (0.594 μA μM−1 cm−2), and wide consecutive linear ranges, respectively. Besides, the proposed method has been effectively employed for the detection of PHY in the various real samples which reveals good recoveries of 95.40–99.17%.

A Nanopipette Supported Oil/Water Interface Sensor for the Kinetics Analysis and Determination of Phenothiazine Derivatives

• A nano-ITIES sensor supported by nanopipette for phenothiazine derivative has been proposed. • The transfer Gibbs energies, relative hydrophilicity and the transfer kinetics of promethazine and chlorpromazine has been analyzed. • Determinations for chlorpromazine and promethazine have been performed, excellent stability and satisfactory recoveries in real drug samples have been obtained. • This strategy established a preferable method to evaluate the permeability of drug ions across biomembrane. Phenothiazine is an intermediate in the synthesis of drugs, and its derivatives, i.e., chlorpromazine (CPZ) and promethazine (PMZ), are both the major tranquilizers. Herein, a nanoscale soft sensor constructed utilizing the interface between two immiscible electrolyte solutions (ITIES) for CPZ and PMZ drugs was introduced. A nanopipette with a 60 nm diameter orifice was used to support the ITIES, and voltammetry and amperometry were used for the qualitative and quantitative determination of these two drugs crossing the liquid/liquid (L/L) interface. Half-wave potentials ( Δ w o φ 1 / 2 ) of 0.107 V and 0.092 V (vs. Δ w o φ 1 / 2 , T E A + ) for PMZ + and CPZ + transfer from water to 1,2-dichloroethane (DCE) were obtained, respectively. Subsequently, the kinetics and effective hydrophilicity of these two drugs were thoroughly investigated. Moreover, there were two calibration curves for the determination results between the current and the concentration range for CPZ + and PMZ + by cyclic voltammetry (the concentrations range from 0.1 to 10 mmol −1 ) and amperometry (the concentrations range from 0.02 to 10 mmol −1 ). Finally, the actual drug recovery for these two drugs ranged from 94.83% to 111.02%, which indicates the accuracy in actual medicine is good. The above work provides a soft nano-liquid/liquid interfacial sensor with applications in drugs, including kinetics studies and drug determination, and many applications in detecting pharmaceutical molecules, cellular secretion and other bioorganic compounds.

Impact assessment of the variables affecting the drug release and extraction of polyethylene oxide based tablets

The overall objective of this research is to investigate the impacts of the polymer's molecular weight and source on the abuse deterrent properties of the PEO-based promethazine hydrochloride (PMZ HCl) tablets. Formulations were manufactured by hot-melt extrusion and direct compression, followed by curing. Thermal and mechanical manipulation techniques were applied and compared to the intact tablets. The prime mechanism of the drug release was found to be represented by the diffusion-controlled mechanism and the first-order model for the direct compressed and the hot-melt extruded whole tablets, respectively. A robust Artificial Neural Network (ANN) model was built, and a significance testing analysis was performed to identify the criticality and the impact of the investigated variables on the % release of the active pharmaceutical ingredient (API). The results showed that the use of the polymer from different suppliers had the lowest impact on the % release per time point. Furthermore, we observed that the tablets produced by hot-melt extrusion had faster release rates than tablets produced by direct compression. Moreover, the extraction studies showed that the % API recovered from the hot-melt extruded tablets was significantly higher than the direct compressed tablets regardless of the polymer molecular weight. The findings were attributed to the polymer's thermal degradation during the hot-melt extrusion process, which caused a reduction in solution viscosity and crystallinity of the polymer. The syringeability studies showed that it was relatively harder to withdraw the solution from the DOW samples; however, the % recovered API was higher than samples containing the polymer from Sumitomo Seika.

Promethazine Downregulates Wnt/β-Catenin Signaling and Increases the Biomechanical Forces of the Injured Achilles Tendon in the Early Stage of Healing

Background: Wnt/β-catenin signaling suppresses the differentiation of cultured tenocytes, but its roles in tendon repair remain mostly elusive. No chemical compounds are currently available to treat tendon injury. Hypothesis: We hypothesized that the inhibition of Wnt/β-catenin signaling would accelerate tendon healing. Study Design: Controlled laboratory study. Methods: Tendon-derived cells (TDCs) were isolated from rat Achilles tendons. The right Achilles tendon was injured via a dermal punch, while the left tendon was sham operated. A Wnt/β-catenin inhibitor, IWR-1, and an antihistamine agent, promethazine (PH), were locally and intramuscularly injected, respectively, for 2 weeks after surgery. The healing tendons were histologically and biomechanically evaluated. Results: The amount of β-catenin protein was increased in the injured tendons from postoperative weeks 0.5 to 2. Inhibition of Wnt/β-catenin signaling by IWR-1 in healing tendons improved the histological abnormalities and decreased β-catenin, but it compromised the biomechanical properties. As we previously reported that antihistamine agents suppressed Wnt/β-catenin signaling in human chondrosarcoma cells, we examined the effects of antihistamines on TDCs. We found that a first-generation antihistamine agent, PH, increased the expression of the tendon marker genes Mkx and Tnmd in TDCs. Intramuscular injection of PH did not improve histological abnormalities, but it decreased β-catenin in healing tendons and increased the peak force and stiffness of the healing tendons on postoperative week 2. On postoperative week 8, however, the biomechanical properties of vehicle-treated tendons became similar to those of PH-treated tendons. Conclusion: IWR-1 and PH suppressed Wnt/β-catenin signaling and improved the histological abnormalities of healing tendons. IWR-1, however, compromised the biomechanical properties of healing tendons, whereas PH improved them. Clinical Relevance: PH is a candidate repositioned drug that potentially accelerates tendon repair.

Mixed Oxime-Functionalized IL/16-s-16 Gemini Surfactants System: Physicochemical Study and Structural Transitions in the Presence of Promethazine as a Potential Chiral Pollutant

The increasing concern about chiral pharmaceutical pollutants is connected to environmental contamination causing both chronic and acute harmful effects on living organisms. The design and application of sustainable surfactants in the remediation of polluted sites require knowledge of partitioning between surfactants and potential pollutants. The interfacial and thermodynamic properties of two gemini surfactants, namely, alkanediyi-α,ω-bis(dimethylhexadecyl ammonium bromide) (16-s-16, where s = 10, 12), were studied in the presence of the inherently biodegradable oxime-functionalized ionic liquid (IL) 4-((hydroxyimino)methyl)-1-(2-(octylamino)-2-oxoethyl)pyridin-1-ium bromide (4-PyC8) in an aqueous solution using surface tension, conductivity, fluorescence, FTIR and 1H NMR spectroscopic techniques. The conductivity, surface tension and fluorescence measurements indicated that the presence of the IL 4-PyC8 resulted in decreasing CMC and facilitated the aggregation process. The various thermodynamic parameters, interfacial properties, aggregation number and Stern–Volmer constant were also evaluated. The IL 4-PyC8-gemini interactions were studied using DLS, FTIR and NMR spectroscopic techniques. The hydrodynamic diameter of the gemini aggregates in the presence of promethazine (PMZ) as a potential chiral pollutant and the IL 4-PyC8 underwent a transition when the drug was added, from large aggregates (270 nm) to small micelles, which supported the gemini:IL 4-PyC8:promethazine interaction. The structural transitions in the presence of promethazine may be used for designing systems that are responsive to changes in size and shape of the aggregates as an analytical signal for selective detection and binding pollutants.

Transition from antagonistic to synergistic interaction in mixed micellar system by increase in alkyl chain length of alkyl trimethylammonium bromide

Herein, the electrical conductivity technique used to measure the critical micelle concentration (cmc) for pure cationic surfactants (Dodecyl/cetyltrimethylammonium bromides) and phenothiazine drug (Promethazine hydrochloride), as well as their different mole fractions in 10−3 ​mol/kg 1-methyl-3-octylimidazolium chloride (C8mim.Cl) at different temperatures. By using the cmc values the regular solution theory used to evaluate the micellar mole fraction for DTAB/CTAB-PMT mixed systems. The clint's model used to calculate the ideal critical micelle concentration (cmc∗) that helps to evaluate the ideal micellar mole fraction for studied mixed systems, both explain the deviation from ideality. In addition, interaction parameter βm helps to confirm the nature of interaction (either antagonistic or synergistic) for the studied systems. The calculated parameters confirm a transition in the binding nature from antagonistic to synergistic with the increase in alkyl chain length of cationic surfactant i.e., component of the binary mixed system. The ease of micellization for the studied systems discussed by the standard Gibb's energy of micellization (ΔGm0), as well as the standard enthalpy and standard entropy of micellization were (ΔHm0) and (ΔSm0), respectively to discuss the stability of the studied systems.