Propranolol Research Articles

Effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/PPARγ pathway in arrhythmic rats

This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/β-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/β-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.

Design and evaluation of propranolol hydrochloride loaded thiolated Zein/PEO electrospun fibrous matrix for transmucosal drug delivery.

Thiolated polymers have garnered wide attention from researchers on mucoadhesive drug delivery. This work explores the thiolation of zein protein using cysteine amino acid via the EDC crosslinker. The optimization of thiolation and purification have been done and confirmed using Ellman's assay and Raman spectra. The thiolated Zein/PEO polymer blend has been appraised for electrospinning to fabricate fibrous matrices. The extent of thiol modification augmented the mechanical properties and adhesion in rabbit intestinal mucosa. In vitro cytotoxicity evaluations such as direct contact assay, MTT assay, and live dead assay performed in RPMI 2650 cells corroborated the non-cytotoxicity of the fabricated matrices with and without propranolol hydrochloride (PL). Detailed drug release studies were conducted in PBS. Drug release in PBS followed the Korsmeyer Peppas model of release. On treating RPMI 2650 cells with the matrix, F-actin and adherens junctional proteins retained integrity, and consequently, drug permeation would proceed through the transcellular transport mechanism. Transepithelial electrical resistance (TEER) measurement of the RPMI 2650 cell monolayer also supported the transcellular transport mechanism. Ex vivo permeation study through porcine buccal mucosa showed 41.26 ± 0.56% PL permeation within 24 h of study. It validated the competence of the electrospun thiolated Zein/PEO matrix for transmucosal drug delivery.

Formulation and Optimization of Propranolol Bilayer Tablets: A Potential Approach for Effective Management of Hypertension

The purpose of this investigation is to formulate and evaluate the antihypertensive drug propranolol hydrochloride sustained-release bilayer tablets. In this formulation, one layer provides a loading dose through the immediate release of the drug and the other layer provides a maintenance dose for up to 12 h through controlled release. Different quantities of polymers such as Kyron T-314, Hydroxypropyl methylcellulose- K4M, and ethyl cellulose were used to make bi-layer tablets by direct compression. The compatibility study of pharmaceutical excipients was conducted through Fourier transform infrared spectroscopy studies and no interaction was found. The pre-compression parameter for the angle of repose, bulk density, tapped density and compressibility index was assessed on the produced granules and the findings were good. The tablets were evaluated for the post-compression parameters for thickness, hardness, friability and in vitro release studies. In vitro dissolution study was approved out for 12 h using United States Pharmacopeia dissolution apparatus I using phosphate buffer of pH 1.2 and 6.8 as dissolution medium. Hydroxypropyl methylcellulose- K4M and ethylcellulose were used in combination in all formulations but optimized formulation propranolol hydrochloride tablet 4 showed a higher rate of drug release up to 12 h as compared to the other formulation and optimized formulations propranolol hydrochloride tablet 4 follows the Higuchi model with non-fickian diffusion based on regression coefficient of the kinetics data of cumulative drug release from the dosage form.

Propranolol for Vascular Anomalies: Efficacy and Complications in Pediatric Patients.

Congenital vascular anomalies are classically subdivided into vascular tumors and vascular malformations. The role of propranolol in the regression of infantile hemangioma (IH), a vascular tumor, is well establishe. This study aimed to analyze the therapeutic efficacy and complications associated with oral propranolol and adjuvant therapy in the treatment of vascular anomalies. A prospective interventional study was undertaken over 10 years duration extending from 2012 to 2022 at a tertiary care teaching institute. All children with cutaneous hemangiomas and lymphatic and venous malformations under 12 years of age, except those with contraindications for administration of propranolol, were included in the study. Out of 382 patients, there were 159 males and 223 females (male: female = 1:1.4). The majority (53.66%) were between ≥3 months and 1 year. There were 481 lesions in 382 patients. There were 348 patients with IH, and 11 were congenital hemangiomas (CHs). There were 23 patients with vascular malformations; lymphatic malformation (n = 19) and venous malformation (n = 4) were present. The size of the lesions ranged from 5 mm to 20 cm; 50.73% were 2-5 cm in size. Ulceration (>5 mm) was the most common complication present in 20/382 (5.24%) patients. Complications related to oral propranolol were seen in 23 (6.02%) patients. Drugs were given for a mean period of 10 months (range from 5 months to 2 years). At the end of the study, 282 (81.03%) out of 348 patients with IH showed an excellent response; 4 (36.36%) patients in the case of CH (n = 11) and 5 (21.74%) patients with vascular malformation (n = 23) showed excellent response. The study validates the use of propranolol hydrochloride as the first-line agent for the treatment of IHs and congenital hemangiomas. It may have an additive role in lymphatic malformations, and venous malformations, as a part of a multimodality treatment approach for vascular malformations.

Propranolol-loaded nanostructured lipid carriers for topical treatment of infantile hemangioma

Oral administration of propranolol hydrochloride (PPL) is a first-line treatment option for infantile hemangioma. However, systemic drug distribution has been associated with severe adverse effects. Thus, this study aimed to investigate the feasibility of using PPL-loaded nanostructured lipid carriers (NLC) for topical drug delivery as a safer alternative for hemangioma treatment. Rosa rubiginosa essential oil was selected as a liquid lipid and possible therapeutic adjuvant. NLC with two different diameters (500 and 900 nm) were prepared and evaluated regarding stability, drug release, skin permeation, and cell activity. The NLC exhibited diameters within the confidence interval of the predictive model (569 ± 87 nm and 824 ± 58 nm), polydispersity index of 0.5, zeta potential close to neutrality, pH 5.5, and entrapment efficiency of 99%. The NLC were stable under refrigeration and controlled PPL release for 12 h, following first-order and Weibull kinetics (coefficient of determination >0.95). In the permeation assays with intact skin, the NLC exhibited a lower drug accumulation in the deeper skin layers, at least 5-fold less than the drug solution, with 19.5 and 12.7 μg cm−2 for the NLC of 500 nm and 900 nm, respectively, versus 88.1 μg cm−2 for the PPL solution. Moreover, no PPL was found from the NLC in the receptor medium the PPL solution resulted in skin permeation of up to 43.4 ± 5.9 μg cm−2. Furthermore, this trend was maintained even when the formulations were applied to a skin model in which hair follicles were blocked. Lastly, PPL-loaded NLC exhibited significant toxic, anti-proliferative, and anti-migratory effects over human brain microvascular endothelial cells superior to the non-formulated drug. In fact, PPL-loaded NLC inhibited cell proliferation by ≥ 50% after 6 days and limited cell migration to approximately 25%, compared to approximately 100% of controls. Thus, topical PPL-loaded NLC proved to be a promising drug delivery system for the topical treatment of infantile hemangioma.

Resolving male infertility that is induced by β-and ca channel antagonist drugs: Propranolol/Verapamil using an optimized nanohybrid formula: Experimental and computational studies

Two major objectives of the current study, the first was to study theoretically the electronic structure of Chitosan-Sodium alginate, Epigallocatechin-gallate (EGCG) and Sodium alginate-EGCG complex using density-functional theory (DFT) calculations. The binding energy (ΔEbind), the atoms in molecules (AIM) theory and the Natural bond orbital (NBO) analysis of Chitosan-Sodium alginate-EGCG complex have been studied in gas and water phases. The second was to investigate the treatment effect of EGCG in normal form and EGCG-loaded chitosan-sodium alginate nanoparticles (EGCG-CS-SA NPs) on the male infertility that was induced in male albino rats by the oral administration of Propranolol Hydrochloride and Verapamil Hydrochloride. Full characterization of the synthesized EGCG-CS-SA NPs were carried out using different techniques. Then eight groups of rats were classified as follows: control negative (A); Propranolol Hydrochloride (B); Verapamil Hydrochloride (C); EGCG normal (D); EGCG nano (EGCG-CS-SA NPs) (E); Propranolol Hydrochloride + EGCG (F); Propranolol Hydrochloride + EGCG-CS-SA NPs (G); and Verapamil Hydrochloride + EGCG-CS-SA NPs (H). The study registered the body weight gain percentage as well the weights of the liver, testes, and seminal vesicles. Malondialdehyde (MDA), glutathione reduced (GSH), and testosterone levels were assessed. The semen analysis was performed, the deoxyribonucleic acid (DNA) damage was detected, and the histopathological sections were examined. The computational study identified that the interaction between chitosan-sodium alginate and EGCG is covalent and electrostatic interactions in nature in the gas and water phases. The results recorded an increase in body weight gain percentage in Propranolol Hydrochloride + EGCG-CS-SA NPs and Verapamil Hydrochloride + EGCG-CS-SA NPs groups but no significant difference (P› 0.05) in organs weight of experimental groups (B, C, D, E, F, G, and H) as compared to control group. In the treated rats (F, G, and H), the MDA decreased significantly, while the GSH increased.The results showed that the formula improved the negative effects of Propranolol Hydrochloride and Verapamil Hydrochloride administration on serum testosterone level, sperm count, motility, percentage of live sperms, and histological structures in the testes and epididymides. Post-administration of EGCG normal and EGCG-CS-SA NPs to Propranolol Hydrochloride and Verapamil Hydrochloride caused no significant difference (P› 0.05) in tail moment value in testes cells as compared to Propranolol Hydrochloride and verapamil Hydrochloride groups. Finally, the herbal nanohybrid formula EGCG-CS-SA NPs was found to be safe and could be used to treat male infertility caused by antihypertensives.

Preparation and evaluation of various formulation effects of the second emulsion on the shape and release profile of propranolol HCl from ethyl cellulose microparticle blends

AbstractThe objective of this study was to investigate and characterize incorporated propranolol HCl (Pro) within ethyl cellulose microparticle blends using the solvent evaporation method. The microparticle blends were prepared with a water‐in‐oil‐in‐water (W/O/W) solvent evaporation method and contained the same drug Propranolol HCl (Pro). The first Pro emulsion (W/O) and second Pro emulsion (W/O) were dispersed in an external aqueous phase, with a dispersion time interval (DTI) of 0 and 60 min. The morphology of the microparticle blends was characterized by SEM. The mean particle size, chord length distribution and chord count of the emulsion droplets/hardened microparticles were monitored by focused beam reflectance measurement (FBRM). The encapsulation efficiency and in vitro drug release in phosphate buffer (pH 7.4) were also investigated. The resulting microparticles were spherical, of two populations. The mean particle size of the microparticle blends ranged from 104.26 μm to 127.64 μm. The encapsulation efficiency was about 76.53% to 78.81% for propranolol HCl in the microparticle blends. FBRM studies showed that the size of the microparticle blends prepared by the W/O/W (Pro) method with DTI 60 min and stirring time 4 h was larger than that of the microparticle blends with DTI 0 min. In vitro drug release studies after 28 days showed that the propranolol HCl release from microparticle blends with DTI 60 min (54.05%) was slower than from microparticle blends with DTI 0 min (73.28%). Based on these data, there is an interaction of the second primary emulsion with hard particles from the first primary emulsion, whereby the second primary emulsion blocked and coated pores on the surface of hard particles from the first primary emulsion. These blocking and coating effects of the microparticles depended on the method and the DTI. In conclusion, novel microparticle blends containing drugs of the same solubility offer high potential for controlled release drug delivery systems. © 2022 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Binary mixture (1:1) of Triton X100 and Propranolol hydrochloride in an aqueous solution of NaCl: Whether mixed micelles are formed, possible clarification in 1H DOSY NMR experiment

Micellisation of the binary mixture (1:1) of non-ionic surfactant Triton X100 and surface-active drug Propranolol hydrochloride is examined in an aqueous solution of NaCl (0.3 molkg−1) in the temperature interval T = (273.15–313.15) K with steps of 5 K. Propranolol hydrochloride has two critical micellar concentrations (cmc) if the solution contains NaCl (0.3 molkg−1), while its binary mixture with Triton X100 (1:1) has one critical micellar concentration. The interaction coefficient (β) between structurally different micellar building units is β > 0, which means that there are antagonistic interactions in the binary mixed micelle, i.e., the molar excess Gibbs free energy is higher than zero, which probably originates from the increase in the degree of hydrophobic hydration when incorporating the naphthalene ring (part of Propranolol hydrochloride) into the Triton X100 micelle. The change of the molar Gibbs free energy of mixing is lower than zero. Thus the driving force for the formation of the binary mixed micelle originates from the entropy of mixing structurally different particles. The Diffusion-Ordered SpectroscopY (DOSY) experiment makes it possible to determine, based on the change (reduction) of the self-diffusion coefficient (D) of a surfactant concerning the D value in the monomeric state, whether the observed surfactant (whose concentration in the solution must be lower than its monocomponent cmc values) with another surfactant particle (from a binary mixture of surfactants) forms a binary mixed micelle. DOSY experiment was performed in an aqueous solution without NaCl. If the total concentration of the examined binary mixture is higher than its critical micellar concentration, it decreases the self-diffusion coefficient of both components, suggesting the formation of the binary mixed micelle. The self-diffusion coefficient of Triton X100 is significantly lower than that of propranolol hydrochloride, indicating that non-ionic surfactant dominates in the binary mixed micelle.

Sodium Alginate-Quaternary Polymethacrylate Composites: Characterization of Dispersions and Calcium Ion Cross-Linked Gel Beads.

The objective of this work was to examine the effect of quaternary polymethacrylate (QPM), a water-insoluble polymer with a positive charge, on the characteristics of the sodium alginate (SA) dispersions and the calcium alginate (CA) gel beads containing propranolol HCl (PPN). The SA-QPM composite dispersions presented the formation of flocculates with a negative charge due to the electrostatic interaction of both substances. The QPM addition did not affect the SA dispersions' Newtonian flow, but the composite dispersions' viscosity enhancement was found. The PPN-loaded CA-QPM gel beads had more spherical than the PPN-loaded CA gel beads. The incorporation of QPM caused a bigger particle size, higher drug entrapment efficiency, and greater particle strength of the gel beads. Despite the similar water uptake property, the PPN-loaded CA-QPM gel beads displayed lower burst release and slower drug release rate than the PPN-loaded CA gel beads. However, the drug release from the PPN-loaded CA-QPM gel beads involved drug diffusion and matrix swelling mechanisms. This study demonstrated that adding QPM into the SA dispersions leads to a viscosity synergism. The CA-QPM gel beads display a good potential for use as a bioactive compound delivery system.

Electrospun Mucoadhesive Zein/PVP Fibroporous Membrane for Transepithelial Delivery of Propranolol Hydrochloride.

Mucoadhesive drug delivery systems have been extensively studied to effectively reduce the limitations of conventional drug delivery systems. Zein and polyvinyl pyrrolidone (PVP) are appraised for mucoadhesive properties. This study focuses on developing a mechanically stable zein/PVP electrospun membrane for propranolol hydrochloride (PL) transport. Fourier transform infrared, Raman spectra, and swelling studies gave evidence for PVP crosslinking, whereas circular dichroism spectroscopy revealed crosslinking of zein owing to the conformational change from α-helix to β-sheet. A 10 h thermal treatment of zein/PVP imparted 3.92 ± 0.13 MPa tensile strength to the matrix. Thermally crosslinked electrospun zein/PVP matrix showed 22.1 ± 0.1 g mm work of adhesion in porcine buccal mucosa tissue. Qualitative and quantitative evaluation of cytotoxicity in RPMI 2650 has been carried out. The in vitro drug release profile of PL from thermally crosslinked zein/PVP best fitted with the Korsmeyer-Peppas model. Immunostaining of β-catenin adherens junctional protein confirmed the absence of paracellular transport through the junctional opening. Still, drug permeation was observed through the porcine buccal mucosa, attributed to the transcellular transport of PL owing to its lipophilicity. The ex vivo permeation of PL through porcine buccal mucosa was also evaluated.

Propranolol hydrochloride induces neurodevelopmental toxicity and locomotor disorders in zebrafish larvae

Propranolol hydrochloride is the first-line drug for the clinical treatment of hypertension, arrhythmia, and other diseases. However, with the increasing use of this drug, its safety and environmental health have received more and more attention. In this study, aquatic vertebrate zebrafish were used as a model to study the toxic effects and mechanisms of propranolol hydrochloride. It was revealed that zebrafish larvae exposed to propranolol hydrochloride showed aberrant head nerve development and locomotor disorders. Additionally, exposure to propranolol hydrochloride could induce oxidative stress, alter the activities of AChE and ATPase, and disrupt the expression of genes involved in neurodevelopment and neurotransmitter pathways. More interestingly, the expression of Parkinson's disease-related genes was altered in zebrafish treated with propranolol hydrochloride. We detected the expression of genes related to the Wnt signaling pathway and found that their expression appeared to be down-regulated. The phenotype of nerve developmental defects and locomotor disorders can be effectively rescued by astaxanthin and Wnt activators. Collectively, the results suggest that propranolol hydrochloride may induce neurotoxicity and abnormal movement behavior with PD-like symptoms in zebrafish larvae.

Theoretical study on the degradation mechanism of propranolol in aqueous solution initiated by hydroxyl and sulfate radicals

In this paper, density functional theory (DFT) calculation was carried out to explore hydroxyl (•OH) and sulfate radicals (SO4•-)-initiated oxidative degradation of propranolol (PRO) in an aqueous solution. It was found that the most favorable pathways for the reactions between PRO and •OH are •OH addition (ADD) reactions related to C1, C2, and C4 sites of PRO and hydrogen atom abstraction (HAA) channels involving C10-H, C11-H, and C13-H bonds. The plausible subsequent reactions of the favorable initial intermediates include hydroxylation, naphthalene ring cleavage, ether bond and CN bonds breakage, and their combination. SO4•- was found to have stronger oxidizing performance than •OH in the aqueous degradation of PRO. Single electron transfer (SET) reaction between PRO and SO4•- is not feasible. Water molecules and dissolved oxygen in water participate in aqueous degradation of PRO.

Natural rubber-based pressure sensitive adhesive as a drug carrier

Natural rubber (NR) has been utilized in several products from its interesting unique properties. This study aimed to develop the pressure-sensitive adhesives (PSA) as the transdermal patches from NR by two-roll mill kneading technique. Hydroxyethyl cellulose (HEC) was blended as a tackifier agent. The propranolol HCl and ibuprofen at different parts per hundred of rubber (phr) were loaded into this developed PSA. The appearance, thickness, crystallinity, contact angle, water sorption and erosion, adhesion, and in vitro drug permeation of these patches were evaluated. The thickness of all patches was in the range of 0.46–1.07 mm. The drug-loaded patches showed diverse unique topographies depended on both type and amount of drug incorporation. From powder X-ray diffraction analysis, the plain NR-PSA showed the amorphous structure, while the halo pattern inserted with sharp drug peaks were observed on drug-loaded PSA. The contact angle of all samples was in the range of 80–90° indicating their hydrophobic surface. However, they displayed an increased % water sorption with the time of soaking. The 2–4 N adhesion force was evident for all fabricated drug-loaded PSAs. The propranolol HCl permeated from PSA notably lower than ibuprofen. The residual of the drugs in patches was about 85–90 %. These results provided the basic physicochemical properties for the further development of PSA as the transdermal patch.[copyright information to be updated in production process]

Влияние агониста бета3-адренорецепторов мирабегрона на активность нейтрофилов венозной крови небеременных женщин

The aim of this paper was to determine the effect of the beta3-adrenergic receptor agonist mirabegron on the free-radical activity of venous blood neutrophils in non-pregnant women. Materials and methods. Using the chemiluminescent method (BChL-07 biochemiluminometer), the parameters of the radical response of venous blood neutrophils in 40 non-pregnant women were determined in different phases of the cycle and on the first day after childbirth with additional cell stimulation with latex particles (0.08 μm). When the noise level was automatically subtracted, the following were recorded: maximum intensity of the synthesis of reactive oxygen species, time to reach the maximum of synthesis intensity, and area under the chemiluminogram curve, reflecting the total synthesis of radical particles over the course of 30 min. These parameters were determined before and after an in vitro introduction of the beta -adrenergic receptor agonist mirabegron (10–6 g/l), beta-adrenergic receptor blocker propranolol hydrochloride (10–6 g/l) and agonist against the background of the blocker into the venous blood. Results. Using the Wilcoxon signed-rank test, we showed an increase in the free-radical activity of neutrophils in women in the follicular phase of the menstrual cycle under the influence of mirabegron for all three evaluated parameters. In the luteal phase, mirabegron significantly increased the rate of reaction development and the total synthesis of radical particles, but did not affect the intensity of production of activated oxygen species. However, no effect was observed on the first day after delivery. The possible mechanism of the revealed mirabegron action is discussed in the article. The authors believe that changes in the activity of venous blood neutrophils under the action of mirabegron may be due to changes in the quantity or sensitivity of beta3-adrenergic receptors in different phases of reproduction.

Design and development of 3D-printed bento box model for controlled drug release of propranolol HCl following pharmacopeia dissolution guidelines

The goal of this study was to develop a 3D-printed bento box model (3D-printed BB) with one or two chambers containing propranolol hydrochloride (PNL) as powder and matrix tablet for controlled drug release at varying times using United States Pharmacopeia (USP) dissolution guidelines. The 3D-printed BBs were made with commercial polyvinyl alcohol filament and a fused deposition modeling (FDM) 3D printer, with varying infill percentages and wall thicknesses. The physicochemical properties of the 3D-printed BBs, including appearance, thickness, size, weight, hardness, swelling, and erosion properties were investigated. The surface and cross-section morphologies of the 3D-printed BBs were characterized using a FESEM. According to FESEM images, the different infill percentages had a significant effect on the internal structure of the 3D-printed BBs’ caps, but a minor effect on the internal structure of their walls. PNL release from the 3D-printed BB began in a pH 1.2 medium, followed by drug release in a pH 6.8 medium. Some formulations of 3D-printed BB could achieve a drug release percentage within all the ranges specified by USP dissolution guidelines. 3D-printed BBs, therefore, have the potential to revolutionize the future of the pharmaceutical industry by facilitating control of the amount of drugs released at predetermined intervals.

Real-time optical imaging of the hypoxic status in hemangioma endothelial cells during propranolol therapy.

Infantile hemangioma (IH) is the most common microvascular tumor of infancy involving the area of head and neck. One of the most important independent risk factors of IH is the hypoxia microenvironment. Fluorescent chemosensor provides a noninvasive intervention, high spatiotemporal resolution, ultrasensitive response, and real-time feedback approach to reveal the hypoxic status of cells. Our research group developed an ultrasensitive fluorescent chemosensor, HNT-NTR, and investigated the potential ability of imaging the hypoxic status of hemangioma-derived endothelial cells (HemECs). In this study, we successfully visualized the propranolol (PRN) treatment in HemECs using NHT-NTR with “Turn-off” sensing method. This chemosensor exhibited high sensitivity and selectivity for optical imaging of hypoxic status with fast responsiveness, real-time feedback and durable photostability of the fluorescent signal. It was also confirmed that HNT-NTR could monitor nitroreductase in vivo. Paramountly, we expected this chemosensor to offer an available optical method for imaging of the hypoxic status and visualizing the therapeutic status of PRN therapy in IH with the hypoxia-imaging capability.

Water-compatible Janus molecularly imprinted particles with mouth-like opening: Rapid removal of pharmaceuticals from hospital effluents.

Pharmaceuticals in hospital effluents, often discharged into the public sewage network without sufficient treatment, have shown negative impacts to the human health and aquatic environment. However, the conventional adsorbents used to remove these micropollutants had several deficiencies, including slow uptake kinetics and poor selectivity. To overcome these challenges, water-compatible Janus MIP particles (J-MIPs) with mouth-like openings were synthesized using seeded interfacial polymerization in this work. Among the series of J-MIPs, the selected J-MIP3 showed fast binding kinetics (∼40s) towards the target pollutant. The theoretical and instrumental analysis suggested that the electrostatic interaction, hydrogen bond and hydrophobic reaction constituted the dominant mechanism for J-MIP3's recognition of target pharmaceutical. Selectivity and robustness tests indicated that the synthetic method was promising in practical application. Finally, the feasibility of the J-MIP3 fixed-bed column in the rapid removal of propranolol (PRO) from hospital effluents was successfully demonstrated. Compared to the activated carbon fixed-bed column, the J-MIP3 fixed-bed column showed at least 7-fold enhancement in its treatment efficiency. To the best of our knowledge, this is the first time that the accelerated mass transfer and fast removal of the pharmaceutical from wastewater have been achieved by the synthetic receptor with asymmetric structure. We believe the present study will open new avenues for the development of multi-functional molecularly imprinted polymers as well as Janus materials in environmental science.

Synthesis of mesoporous P‑doped carbon and its application in propranolol drug removal: Characterization, kinetics and isothermal studies

A novel P‑doped mesoporous carbon (PMC) was prepared from sucrose, a natural source, using a hard template based on silica nanoparticles. The new PMC was characterized by SEM, TEM, XRD, N2 physisorption, Raman, XPS, and FT-IR. The analysis confirmed the tridimensional structure of PMC, which showed a high surface area of 830 m2.g−1 and a pore volume of 1.4 cm3.g−1. XPS analysis determined the phosphorus content of 4.1 %, mainly due to the functional groups of C3-PO and C−P(O)(OH)2/C2 −P(O)(OH). The new material was used to remove the drug propranolol (PRO) from water. PMC could remove PRO in 10 min, achieving a high removal capacity of 287 mg.g−1, corresponding to 99 % of removal efficiency. The kinetic and equilibrium data were best described by pseudo-second order kinetic and BET isothermal models, suggesting multilayer adsorption where the first layer of PRO molecules strongly binds to the PMC surface, and subsequent layers are formed over the first one. The proposed mechanism of PRO adsorption is based on the chemisorption in C−P(O)(OH)2/C2 −P(O)(OH) acidic groups of PMC, physisorption through hydrogen-bonding, electrostatic and π − π interactions. PMC has proven to be a promising adsorbent for the uptake of propranolol from water.

Influence of Prunus domestica gum on the release profiles of propranolol HCl floating tablets.

Propranolol hydrochloride is a beta-blocker used for the management and treatment of hypertension, angina, coronary artery disease, heart failure, fibrillation, tremors, migraine etc. The objective of the present study was to design Propranolol Hydrochloride floating tablets by direct compression method and to explore the role of a new gum as a matrix former. A 22 full factorial design was selected for the present study. Prunus domestica gum and HPMC (K4M) were used as independent variables, swelling index and drug dissolution at 12 hours as dependent variables. Formulations were subjected to pre- and post-compression tests that showed good micromeritics and buoyancy characteristics (Carr’s index 11.76%–14.00%, Hausner’s ratio 1.13°–1.16°, angle of repose 22.67°–25.21°, floating lag time 56–76 seconds, total floating time 18–25 hours and swelling index 59.87%–139.66%). The cumulative drug release in 0.1 N HCl at 12 hours was 72%–90% (p<0.05). Weibull model was found to be the best fit model (R2>0.99) among all other studied models. Multiple regression showed a significant effect of Prunus domestica gum and HPMC K4M on the swelling index and dissolution profiles of propranolol HCl (p<0.05). On the basis of better in-vitro performance and cost-effectiveness, formulation F4 was the best formulation. It is evident from the results that Prunus domestica gum possesses excellent drug release retardant potential for the floating drug delivery system and this new gum should be further explored alone or with other natural and synthetic polymers in future studies.

Drug-Polymers Composite Matrix Tablets: Effect of Hydroxypropyl Methylcellulose (HPMC) K-Series on Porosity, Compatibility, and Release Behavior of the Tablet Containing a BCS Class I Drug.

The purpose of this research was to see how the physicochemical properties and porosity of matrix tablets containing various types of hydroxypropyl methylcellulose (HPMC) K series affected the release of propranolol hydrochloride (PNL). PNL is a class I drug (high solubility and permeability) according to the Biopharmaceutics Classification System (BCS), making it an excellent model drug used for studying extended-release drug products. The direct compression method was used to prepare the HPMC-based matrix tablets. PNL and the excipients were found to be compatible using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). The surfaces of all the compressed HPMC-based matrix tablets were rough, with accumulated particles and small holes. The compressed HPMC-based matrix tablet porosity was also determined by using mercury porosimetry. The compressed HPMC-based matrix tablets made of low viscosity HPMC had tiny pores (diameter < 0.01 μm). The shorter polymeric chains are more prone to deformation, resulting in a small pore proportion. The compressed HPMC-based matrix tablets sustained the release of PNL for over 12 h. The release exponent values (n), which reflect the release mechanism of the drug from the tablets, ranged from 0.476 to 0.497. These values indicated that the release was governed by anomalous transport. The compressed HPMC-based matrix tablets have the potential for a sustained release of PNL.