Effect of drug solubility, polymer, and filler on drug release from modified-release matrix tablets in hydroethanolic media.

ABSTRACT Environmentally relevant water matrices contain multiple organic contaminants, increasing complexity in multicomponent adsorption systems. This study investigates continuous fixed-bed adsorption of caffeine (CAF), atenolol (ATL), and propranolol (PRO) onto granular activated carbon (GAC) under single- and multicomponent conditions. Breakthrough data were analyzed using a Bayesian framework to model adsorption dynamics and quantify parameter uncertainty. Single-component experiments identified optimal conditions (C0POL = 60 mg.L−1, Q = 4 mL.min−1 and W = 0.5 g), achieving > 95% removal and capacities of 8.81 mgATL.gGAC −1 for ATL and 8.04 mgPRO.gGAC −1 for PRO, with saturation times of 66 and 52 min. In multicomponent operation, competitive adsorption reduced performance, yielding optimal time of 35 min with removals > 95% for CAF and ATL and 84% for PRO. Adsorption capacities decreased by ~57%, reaching 3.59 mgCAF.gGAC −1 (CAF), 3.93 mgATL.gGAC −1 (ATL), and 3.36 mgPRO.gGAC −1 (PRO), confirming distinct adsorption dynamics among the compounds. Logistic and Gompertz models described breakthrough curves, with Gompertz outperforming (R2 ≥ 0.97) by better capturing asymmetric S-shaped profiles. Bayesian analysis indicated faster breakthrough for CAF and ATL and delayed saturation for PRO due to stronger GAC interactions. Overall, empirical – Bayesian framework provides a robust and interpretable tool for multicomponent adsorption in fixed-bed water treatment under realistic conditions.

Infantile hemangioma (IH) is a benign vascular neoplasm, occurring in 4–10 % of newborns and requiring timely therapy in cases of complicated progression. Currently, propranolol is recognized as the "gold standard" for IH treatment due to its proven efficacy and safety. However, in the Russian Federation, there are no readily available dosage forms (DFs) of propranolol for children, which creates a significant problem for pediatric practice. In this regard, the development of a PF that ensures accurate dosing and ease of use in children is relevant. The aim. To develop the composition and technology for obtaining orodispersible mini-tablets (OMT) of propranolol hydrochloride for children using the Quality by Design (QbD) approach. Materials and methods. The active pharmaceutical substance of propranolol hydrochloride and excipients were used: mannitol, microcrystalline cellulose 102 (MCC 102), crospovidone (CPV), sodium saccharin dihydrate, sodium stearyl fumarate (SSF), and colloidal silicon dioxide. The composition development was carried out using the QbD methodology, with experimental design planned using the Mixture Design (MD) method. The independent variables were the content of MCC 102, CPV, and SSF. OMT with a diameter of 3 mm were obtained by direct compression. The tablet blend and OMT were tested according to the methods presented in the State Pharmacopoeia of the Russian Federation, XV edition: flowability, bulk density and tapped density, crushing strength, friability, disintegration, and mass uniformity. The dose uniformity of the optimized composition was determined by HPLC. Results. During the first stage, the target quality profile of the OMT was determined. In accordance with this, critical quality attributes (CQAs) were established: for the powder blend – flowability, bulk density, tapped density; for the OMT – crushing strength, disintegration, friability, and dose uniformity. A composition was developed and optimized, which allowed the required values for all CQAs to be achieved. Statistical analysis revealed significant inter-component interactions affecting the crushing strength and disintegration of the OMT. Conclusion. The composition and technology for obtaining orodispersible mini-tablets of propranolol hydrochloride have been developed.

Reproductive well-being is the foundation of any enterprise's reproduction. The success of livestock farming depends on the quality of the offspring and the preservation of the productivity of the breeding stock. The postpartum period plays a crucial role in maintaining the physiological health of sows. The farrowing process involves the mobilization of all the mother's body systems and the expenditure of significant energy. The purpose of the study is to conduct a comparative assessment of the effectiveness of myotropic drugs used with carbetocin in the therapeutic treatment of highly productive sows with signs of postpartum uterine and mammary gland inflammatory diseases. To achieve this, the frequency of drug administration, the milk production of sows, the survival rate of piglets at weaning, the duration of the non-productive period, and the fertility rate were analyzed. To conduct the experiment, 3 groups (n=10) of similar sows with clinical signs of the disease were formed. Similar groups were formed for the diagnosis of postpartum endometritis. In the first group of sows, the prolonged drug Rutocin (with the active ingredient carbetocin 0.07 mg/ml) was used at a dosage of 1.0 ml/head. In the second group, the sows were administered Uteroton (based on propranolol hydrochloride 5 mg/ml) at a dosage of 5 ml/head. In the third group, the sows were treated with the hormonal drug Oxytocin at a dosage of 20 IU/head. The results of the conducted studies showed that the duration of treatment is reduced and reproductive indicators are improved when using carbetocin in the treatment of sows with postpartum dysgalactia and postpartum endometritis.

Many clinically used drugs are amphiphiles, yet the effect of their amphiphilicity on their therapeutic activity is poorly understood. As cell membranes are the first barrier a drug encounters on route to its site of action, we propose that an amphiphilic drug's membrane activity will impact its clinical efficacy. Comprehensive quantitative detail on the membrane interactions of the amphiphilic β-blocker drug, (±) propranolol has been investigated, using a synergistic combination of surface area-pressure measurements, ellipsometry, Brewster angle microscopy and selective H/D contrast variation neutron reflectometry, and using Langmuir monolayers comprising zwitterionic, 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) alone and with 30mol% of negatively charged, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-1'-rac-glycerol sodium (POPG). The interaction of propranolol with the lipid monolayers was resolved in terms of changes in lipid morphology, the extent of lipid loss from the membrane, and the drug's favoured location and orientation within the membrane. Propranolol is proposed to interact with the lipid monolayers in three stages: (1) electrostatic binding to the lipid head groups, (2) drug-mediated lipid loss from the membrane, and (3) the re-organisation of the drug's hydrophobic region within the membrane lipid chains. At steady state, and regardless of lipid packing, the monolayer contains more drug than lipid molecules. Further, the presence of negatively charged POPG does not enhance the cationic drug's interactions with the monolayer, most likely due to the differential solubilisation of membrane lipid in the aqueous subphase. Significantly, these results demonstrate how a drug's amphiphilic nature can determine its membrane activity and thereby impact its clinical efficacy.

The contamination of ecosystems, specifically aquatic ecosystems, has emerged as a substantial concern in recent decades. This is mostly owing to the extensive growth of large industries that not only promote societal advancements but also impose adverse effects on the environment. Azure A (AA) and Azure B (AB) are the cationic dyes commonly employed in industrial and biomedical fields as intermediates in the production of several pharmaceuticals and as mediators for electrochemical biosensing, and indigo carmine (IC) is an anionic dye used in the textile industry for dyeing. Micropollutants such as pharmaceuticals, propranolol hydrochloride (β-blocker) (PPH) are the pollutants in the subject of discussion. In this research, the efficient degradation of AA (91%), AB (84.6%), IC (87.3%) and PPH (>80%) by the CuWO4 photocatalyst is highlighted. Both the dye and drug degradations followed pseudo-first order kinetics. CuWO4 catalyst is used to alleviate the impact of the environment on its ecosystem as a photocatalyst with ultraviolet (UV) irradiation of pollutants (AA, AB, and PPH). For the analysis of pollutant decomposition, UV-visible absorption spectroscopy and high-performance liquid chromatography (HPLC) are employed. This study highlights the potential of nanomaterial-based photocatalysis as a viable and effective method for sustainably mitigating water pollution.

Propranolol Hydrochloride, a non-selective β-adrenergic receptor antagonist originally developed for cardiovascular disorders, has attracted growing interest as a repurposed therapeutic candidate in oncology. Increasing experimental and translational evidence indicates that β-adrenergic signaling plays a pivotal role in tumor progression by linking chronic sympathetic nervous system activation to molecular pathways governing proliferation, angiogenesis, immune evasion, invasion, and metastatic spread. By competitively inhibiting β1- and β2-adrenergic receptors, propranolol interferes with catecholamine-mediated cAMP–PKA and EPAC signaling cascades, thereby modulating transcriptional programs associated with VEGF expression, matrix metalloproteinase activation, inflammatory cytokine production, epithelial– mesenchymal transition, and stress-induced immune suppression. Preclinical investigations across multiple tumor models demonstrate that propranolol can attenuate tumor growth, suppress angiogenesis, reduce metastatic colonization, and enhance anti-tumor immune responses. Importantly, its anti-cancer activity appears most pronounced in stress-responsive and highly vascular tumors, and in the perioperative setting where adrenergic surges may facilitate micrometastatic dissemination. Propranolol has also shown synergistic interactions with conventional chemotherapeutics, targeted agents, radiotherapy, and immune checkpoint blockade, supporting its development primarily as a co-adjuvant rather than a standalone cytotoxic therapy. The extensive clinical experience, affordability, and mechanistic plausibility of Propranolol Hydrochloride represents a compelling candidature for oncologic repurposing. Future directions should integrate biomarker-guided trial designs, combination regimens, advanced tumor-targeted delivery systems, and systems-biology or artificial intelligence-based repurposing pipelines to refine therapeutic positioning. Collectively, current mechanistic, preclinical, and emerging clinical data justify rigorous evaluation of Propranolol as a multi-pathway modulator in contemporary cancer therapy.

Memory deficits in temporal lobe epilepsy severely impair quality of life, yet effective therapeutic strategies remain limited. Vagus nerve stimulation (VNS), an FDA approved treatment for drug resistant epilepsy, has demonstrated beneficial effects on cognition, but the underlying mechanisms are unclear. VNS activates the locus coeruleus norepinephrine (NE) system, and hippocampal β-adrenergic receptors (β-AR) are critical for memory formation and synaptic plasticity. In this study, we used a pilocarpine (PILO) induced memory impaired rodent model to investigate whether VNS improves memory and hippocampal synaptic plasticity via NE/β-AR signaling. Memory impairment was induced in rats using PILO. VNS was administered to PILO-treated rats for 2 weeks via electrodes implanted on the left cervical vagus nerve (parameters: 1 mA, 30 Hz, 250 µs pulse width; 2 h daily). Following VNS treatment, rats underwent contextual fear conditioning (CFC) and long-term potentiation (LTP) testing. Protein expression of NE, β-AR, and downstream signaling molecules (protein kinase A and CaMKII) was quantified. To verify pathway specificity, the β-AR antagonist propranolol (PR) was administered RESULTS: PILO-treated rats exhibited significant memory deficits and impaired LTP compared to controls. VNS treatment markedly improved CFC performance and restored hippocampal LTP in PILO rats. Molecular analysis revealed VNS increased hippocampal NE release and upregulated β-AR and downstream signaling molecules PKA expression. Administration of β-AR antagonist PR prior to VNS abolished these enhancements in memory and synaptic plasticity. The enhancement of hippocampal LTP and memory by VNS is associated with the hippocampal NE/β-AR signaling pathway, indicating a potential therapeutic mechanism for VNS in memory related disorders.

Objective This study was performed to appraise the effect of modulation of formulation pH and abdominal pH on the pharmacokinetics (PK) of the selected compounds from different drugs of the Biopharmaceutics Classification System (BCS) when administered via cassette dosing in rats. Methods Pharmacokinetics of four different BCS class drugs viz. propranolol HCl, diclofenac sodium, atenolol, and acetazolamide (BCS-I, II, III, and IV, respectively) in different formulation pH conditions and different abdominal pH conditions were evaluated. The animal groups were dosed orally. Results Propranolol HCl exhibited a significant increase in area under the curve (AUC0–last) when the alimentary canal pH was modulated to acidic (195%), and a significant increase in maximum concentration at a given time point (C max) (102%) for formulation with basic pH in healthy animals. Diclofenac exhibited a significant increase in AUC0–last when the alimentary canal pH was modulated to acidic (95%), and a significant decrease in C max (55%) for formulation with basic pH in healthy animals. Atenolol displayed a substantial increase in AUC0–last in basic pH conditions in the alimentary canal (38%), and a significant decrease in AUC0–last (49%) for basic pH formulation in healthy animals. Acetazolamide demonstrated a considerable increase in AUC0–last when alimentary canal pH was modulated to basic (55%), and a substantial enhancement in AUC0–last (39%) for acidic pH formulation in healthy animals. Conclusion The results suggest that both alimentary canal conditions with acidic and basic pH and formulation with acidic and basic pH have a considerable influence on the PKs of different compounds not only based on their acid dissociation constant (pKa) but also independently on the pH in the area of absorption in the alimentary canal and salt form of the compound.

Transdermal drug delivery represents an important strategy in personalized medicine, offering advantages such as avoidance of first-pass metabolism, improved adherence, and sustained plasma concentrations. In compounding practice, the assignment of scientifically justified beyond-use dates (BUDs) requires robust evidence of both physicochemical stability and microbiological quality. This study evaluated the chemical and antimicrobial stability of compounded transdermal formulations containing dehydroepiandrosterone (DHEA, 0.1-10.0%), estradiol hemihydrate (0.01-2.0%), progesterone (1.0-20.0%), and propranolol hydrochloride (0.1-5.0%) prepared in Pentravan®. Stability-indicating UHPLC methods were developed and validated for each active pharmaceutical ingredient (API), and forced-degradation studies confirmed method specificity. Formulations were stored at room temperature and analyzed over 180 days, with acceptance criteria defined as 90-110% of labeled content. Antimicrobial effectiveness testing (AET) was performed according to USP <51> at initial and final stability time points. All analytical methods met validation criteria for specificity, linearity (r > 0.99), precision (CV < 5%), and accuracy (98-102%). Estradiol (0.01% and 2.0%), progesterone (1.0% and 20.0%), propranolol hydrochloride (0.1% and 5.0%), and DHEA 10.0% remained within specification for 180 days. DHEA 0.1% demonstrated significant potency loss at 180 days, supporting a BUD of 150 days. No relevant physical instability was observed, and all formulations complied with USP <51> antimicrobial effectiveness requirements throughout their assigned BUDs. These findings demonstrate that Pentravan® supports extended BUDs of up to 180 days for multiple clinically relevant transdermal APIs while maintaining chemical stability and preservative efficacy. Concentration-dependent stability was observed for DHEA, reinforcing the importance of formulation-specific evaluation when assigning BUDs in compounded preparations.

Sodium Carboxymethyl Cellulose (NaCMC) is frequently employed in pharmaceutical formulation. Nevertheless, there are potential interactions between NaCMC and specific drugs, which may have an impact on the stability or bioavailability of those drugs.The purpose is to study the effect of drugs with different charges, anionic Sodium Carboxymethyl Cellulose (NaCMC), excipients, and other parameters on shape, size, and drug release from controlled release matrices of three different drugs and the kinetics of drug release were investigated. Three models of drug matrices (Flurbiprofen, naproxen sodium, and propranolol hydrochloride) were prepared using the direct compression technique with different ratios of sodium carboxymethyl cellulose, other excipients, and surfactants of various solubility and charges. These were used to compare drug release from the matrices in simulated intestinal fluid pH = 7.4 and simulated gastric fluid pH = 1.2. The size and shape changes of the matrices were investigated when these tablets were placed in simulated gastric fluid and simulated intestinal fluid. The mechanisms of drug release were analyzed using different models and equations. Sodium Carboxymethyl Cellulose (NaCMC) had the most significant effect on controlling drug release, swelling rate, size, and shapes of the matrices of the three drugs, regardless of their solubility. The pH of the dissolution medium, surfactants and other excipients, charge, and solubility of the drug also influenced drug release, tablet size, and shape of the different formulations. The swelling rate of the different matrices was constrained only by NaCMC. The ratio of anionic NaCMC primarily controlled the release rate of drugs. The shape and size of the matrices, according to the solubility and charge of these drugs. Other excipients, such as surfactants, lactose, and magnesium stearate, affected the release rate of the drugs, shape and size of the matrices but did not influence their swelling rate.

Approximately 10% of the patients with infantile hemangioma (IH) may exhibit resistance to propranolol (PRN) therapy, and thus alternative strategies are required. Our previous studies reported that oxymatrine (OMT) could inhibit the growth of hemangiomas, however the underlying pharmacological actions have not been fully addressed. In this study, a murine IH model was constructed by implantation of EOMA cells into nude mice. OMT was administrated (50mg/kg; i.p) for 21days. Metabolic changes were examined by proteomics and metabolomics, followed by in vitro experimental validation using EOMA cells. OMT significantly suppressed the growth of hemangioma in vivo without significant adverse effects. A total of 869 differentially expressed proteins and 38 metabolites were identified. In addition to canonical apoptosis regulation, OMT also caused significant metabolic disturbances, particularly in purine and pyrimidine metabolism. Furthermore, ferroptosis may be involved in the therapeutic effect of OMT. In the validation experiments in vitro, we found that OMT dose-dependently reduced the viability of EOMA cells, concomitant with increased production of lipid reactive oxygen species (ROS) and Fe2 + accumulation. In conclusion, these findings suggested that treatment with OMT could suppress the growth of hemangiomas through metabolic disturbances and inducing ferroptosis, which may provide new insights to the management of IH.

Anxiety disorders, characterized by overwhelming fear, affect more than 30% of the global population. Recent evidence indicates that antihypertensive medications could offer symptomatic relief for anxiety, supporting their potential for repurposing. The objective is to investigate the anxiolytic-like effects of an enalapril formulation. 60 Swiss mice (30 ± 5 g, aged 6-8 weeks) were randomly assigned to groups and received oral treatments with either vehicle (10 mL/kg), diazepam (DZP, 5 mg/kg), reference enalapril (ENAR), enalapril formulation (ENAF), losartan (LOS), or propranolol (PRO), each at a dose of 10 mg/kg. After 60 minutes, the animals were exposed to 5 minutes of exploratory activity in the open field, elevated plus maze (EPM), light-dark box (LDB), and a minute of rotarod. One-way ANOVA demonstrated differences for the total crossing (p=0.0001), freezing time (p=0.0001), number of rearing (p=0.002), time spent (p=0.002), and crossing at the center (p=0.0001) of the open field. Unlike in the rotarod (p>0.05), the ENAR, ENAF, LOS, and PRO elicit increases (p<0.05) in the total number of arm entries and time spent on the open arms of EPM while increasing the number of transitions (p<0.05) and time spent in the light area of the LDB (p=0.001). In silico screening suggests stability of interaction with several amino acid residues overlapping with the flumazenil binding site, with the binding energy (ΔE) = -22.59kcal/mol towards the benzodiazepine binding site (flumazenil ΔE = -43.92kcal/mol). The repositioning of drugs available to the population is an interesting approach toward the discovery of alternative or add-on treatments for anxiety. Ongoing resort to repurposing, reusing, reprofiling, and rediscovery of "old" drugs for a new indication seems to be an interesting way out of failures, the expensive and slow pace of new drug discovery. Enalapril demonstrates anxiolytic-like properties, further insights into the GABAergicrenin- angiotensin-aldosterone mechanistic hypothesis.

Schizophrenia is a chronic, complex and severs psychiatric disorder that impacts men and women globally. The combined use of atypical antipsychotics; risperidone (RSP), and antidepressants medications; duloxetine hydrochloride (DLX), has grown more clinical significance in cutting edge treatments of complex psychiatric conditions like schizophrenia. This research targets to develop an environmentally harmonious, selective, and accurate TLC method to measure the levels of both DLX and RSP in spiked human plasma samples. A mixture of methanol, ethylacetate, and 33% ammonia solution (6: 4: 0.2, by volume) was successfully utilized as a solvent system to separate the proposed components. A UV-scanning wavelength of 230 nm was used for detection. An internal standard; propranolol (PRP); was used to account for small variations in the samples. The resulting retardation factors (Rf) were 0.02, 0.32, 0.46 and 0.59 for plasma, DLX, PRP and RSP, respectively. The linearity ranges were 0.04–0.4 and 0.1–0.6 µg band− 1 for DLX and RSP, respectively. The suggested method’s environmental safety was evaluated using five tools and the results showed good greenness and blueness method’s characteristics. Additionally, the method’s figures of merits were within the accepted criteria, according to the US-FDA bio-analytical guidelines. Furthermore, drug-drug interactions (DDI) evaluation was conducted using web-based DDI tool to examine the interaction manifestations and to verify safety and therapeutic effectiveness of this combination.Graphical abstract

The development of advanced macromolecular systems with tailored structural and functional properties is a key objective in modern materials science, particularly for biomedical applications such as targeted drug delivery. In this study, hydrogel (HG), a polymer-based formulation, was investigated as a functional carrier for the enhanced intradermal and transdermal delivery of propranolol hydrochloride (PRO-HCl), a highly water-soluble model compound, and its potential was compared to other vehicles easily obtained by pharmacists: ointment (OM), liposomal cream (LCR), and microemulsion (ME). The formulations were characterized by their physicochemical and rheological characteristics, and evaluated in vitro and ex vivo using vertical diffusion cells equipped with synthetic membranes, intact porcine skin, and skin pretreated with solid microneedles (MNs). The HG formulation exhibited superior release performance (2396.85 ± 48.18 μg/cm2) and the highest intradermal drug deposition (19.87 ± 4.12 μg/cm2), while its combination with MNs significantly enhanced transdermal permeation (p = 0.0017). In contrast, the synergistic effect of MNs and ME led to a pronounced increase in drug accumulation within the skin (up to 60.3-fold). These findings highlight the crucial role of matrix composition and properties in modulating molecular transport through biological barriers. The study demonstrates that polymeric HGs represent versatile, functional materials with tunable structural and mechanical features, suitable for controlled release and potential systemic delivery applications.

Interplay and selectivity of selected pharmaceuticals and organic contaminants adsorption onto magnetic biochar: Mechanistic insights.

This study presents the development of 3D-printed shellac-baseddevices designed for site-specific intestinal delivery of bioactivecompounds. The devices were fabricated using fused deposition modeling(FDM) 3D printing technology, employing a shellac filament plasticizedwith 20% w/w poly­(ethylene glycol) 10000 (PEG 10000). The influenceof structural parametersspecifically base thickness (0.5–2mm) and lateral wall thickness (1–2 mm)on mechanicalperformance, disintegration behavior, and release kinetics was systematicallyevaluated using propranolol hydrochloride as a model bioactive compound.Characterization via scanning electron microscopy (SEM), mechanicaltesting, and thermal analysis confirmed the successful fabricationof devices with a consistent morphology and robust mechanical properties.Increased thickness notably enhanced the mechanical strength and modulatedthe release profiles. Disintegration and dissolution testing demonstratedthat thicker devices resisted acidic degradation while enabling timelyrelease under simulated intestinal conditions. These results underscorethe versatility of shellac-based 3D-printed platforms for precise,delayed, and site-specific intestinal releasenot only forpharmaceutical agents but also for sensitive macromolecules, probiotics,enzymes, and nutraceuticals requiring protection from gastric degradation.

The aim of current examination was to formulate propranolol hydrochloride (PHCL) loaded buccal films by combining polyvinyl alcohol with guar gum using solvent casting process. The formulated films were assessed for a variety of measures including physical evaluation, in vitro drug permeation, in vitro drug release and ex vivo permeation studies. The prepared PHCL loaded films demonstrated homogeneous surface, and the weight uniformity of prepared films was noted in the range of 160 ± 0.29 mg to 169 ± 0.32 mg. The thickness and swelling index of fabricated films were found in the range of 0.132 ± 0.013 mm to 0.264 ± 0.011 mm and 38.73 ± 1.02% to 46.99 ± 1.92%, respectively. The pH of all developed films was near to neutral (pH 6.41 ± 0.71 to pH 6.59 ± 0.91). The folding endurance and drug content of all prepared films were within the range of 74.33 ± 4.04 to 150.00 ± 2.00 and 91.38 ± 0.71% to 97.34 ± 0.13%, respectively. The formulation F2 exhibited maximum in vitro drug permeation (85.11 ± 4.26%) across egg shell membrane, in vitro drug release of 96.66 ± 6.01% and ex vivo drug permeation of 87.36 ± 3.80% across buccal mucosa. The findings of ex vivo permeation through buccal mucosa exhibited that the drug permeation rate was sustained for 360 minutes. A buccal film containing PHCL shows tremendous potential for systemic administration. In addition to circumventing hepatic first-pass metabolism, this method has the advantage of minimizing side effects. To ensure the efficacy of the prepared formulation, further studies in an animal model are recommended.

The consumption of pharmaceuticals during the COVID-19 pandemic increased significantly. As such, over-the-counter drugs such as acetaminophen (ACT), ibuprofen (IBU), metoprolol (MET), and propranolol (PRO) were among the pharmaceuticals that were widely used to contain COVID-19 symptoms. Therefore, this study investigated the occurrence of ACT, IBU, MET, and PRO in wastewater and river water systems, focusing on two provinces in South Africa (Gauteng (GP) and KwaZulu-Natal (KZN)). Generally, WWTP influents had the highest concentrations in both provinces. ACT, MET, and PRO were frequently detected compared to ibuprofen, particularly in KZN, during the second wave of the COVID-19 pandemic. However, a low detection occurred during the fourth wave of the COVID-19 pandemic. The concentrations of ACT, IBU, MET, and PRO in influent wastewater samples ranged from ND-480 µg/L, ND-54.1 µg/L, ND-52.8 µg/L, to ND-13.1 µg/L, respectively. In comparison with influent samples, ACT, IBU, MET, and PRO concentrations of effluent wastewater samples were generally at lower concentration levels: ACT (ND-289 µg/L), IBU (ND-36.1 µg/L), MET (ND-13.9 µg/L), and PRO (ND-5.53 µg/L). The removal efficiencies of the selected pharmaceuticals in KZN WWTPs ranged from 6.1 to 100% and −362.6 to 100% in the GP province. The ecological risk assessment results showed a low to high ecological risk against fish, Daphnia magna, and algae due to the presence of these pharmaceuticals.

The incidence and mortality of colorectal cancer (CRC) have increased globally. Several therapeutic approaches have been suggested to address this health issue, in addition to classical methods. Propranolol (PRO) is a beta-blocker that was repurposed to treat infantile hemangiomas, and its anti-tumor activity has been reported. This study aimed to investigate the effects of PRO in a panel of CRC cell lines and its potential impact when combined with chemotherapy. The effects of PRO on cell cytotoxicity, cell morphology, colony formation, cell death induction, cell cycle, mitochondrial and intracellular reactive oxygen species (ROS), and migration were measured in all cells. CompuSyn software was utilized to assess the possible synergistic or additive interaction in the combined treatment. The results showed that PRO suppressed cell proliferation, altered cell morphology, inhibited colony formation, induced apoptosis, altered cell cycle and ROS generation, and inhibited the migration of treated cells in a cell-type-specific, time-dependent, and dose-dependent manner compared with the control. HT-29 was the most sensitive cell line to PRO in terms of cytotoxicity, apoptosis, cell cycle arrest, and ROS generation, while SW-480 was the most sensitive in terms of migration inhibition. Moreover, the PRO and capecitabine combination exhibited a synergistic effect and induced mitochondrial apoptosis in metastatic CRC cells. The data suggest that PRO could be a promising adjuvant therapy for primary and advanced CRC. This study identified variations between CRC cell lines in response to PRO, which may be related to their genetic and epigenetic differences. In addition, the findings highlight the potential of combination strategies to improve therapeutic outcomes in metastatic CRC.