Abstract This is a commentary manuscript, which aims to carry out a critical analysis of the effects of Pharmaceutical Care (PC) without the continuity of the service by healthcare professionals. PC has proven to be a very effective practice for improving pharmacotherapy for medicine users. In Brazil, it is noticeable that in the vast majority of cases, PC is carried out by professionals who are already working within the healthcare systems under the supervision of researchers affiliated with universities, for the purpose of research and data collection. When the research ends there is no continuation of the service, which hinders its continuous implementation and the establishment of a connection with the community. It was observed that after discharge from pharmacotherapeutic monitoring, due to the interruption of the service, there was a deterioration in the clinical and laboratory parameters of individuals with chronic diseases. Therefore, it is clear that PC needs to be implemented not only for research purposes, but also in the “real world”, so that it is long-lasting and permanent with the monitoring of the patients using medication.

Abstract This study was aimed to determine occupational and non-occupational exposure to benzene, toluene p-m-o-xylene (BTEXs) and butyl-acetate (nBA). The aim of this work was to develop a simple, sensitive, and reliable chromatographic method using urine, a non-invasive human sample. The method was applied to samples collected from furniture spray workers (n=53) who are at risk of exposure to BTEXs and nBA and office workers (n=51) who have no known exposure risk. Method validation tests, include the sensitivity (LOD≤0.018 ng/mL), precision (RSD≤4.1), accuracy (RE% (-3.9)-4.7), recovery (96.1-103.8%) and linearity (r2≥0.999). Urinary benzene (1.77 vs 1.23 ng/mL, exposed-control, respectively), toluene (51.22 vs 0.77 ng/mL), ethylbenzene (9.25 vs 6.69 ng/mL), para-xylene (1.73 vs 0.62 ng/mL), meta-xylene (2.58 vs 1.20 ng/mL), ortho-xylene (1.61 vs 0.88 ng/ mL), and butyl acetate (33.14 vs 1.63 ng/mL) concentrations were determined in the exposed and control group samples. Significant correlations were found between benzene (p=0.286*), ethylbenzene (p=0.552***) and o-xylene (p=0.292*) levels and smoking status in samples belonging to the control group. The occupationally-exposure-risk group samples have significantly higher BTEXs and nBA concentrations than the control (p<0.001). It was determined that smoking was a significantly effective factor in exposure to benzene, ethylbenzene and o-xylene in the control group.

Abstract A significant increase in self-medication was observed during the SARS-CoV-2 pandemic, especially among university students due to their higher level of knowledge and awareness, making them more prone to self-medication. Therefore, in this scoping review we aimed to understand the profile of medications used for self-medication among university students during the pandemic, both for COVID-19 prevention and other reasons. We followed the PRISMA-ScR guidelines in conducting the review. The PICo guiding question was, “What is the profile of medications used for self-medication during the COVID-19 pandemic among university students?” Searches were conducted in the Scielo, PubMed, Embase, EBSCOhost, Web of Science, Scopus, BVS, Google Scholar, and CAPES databases based on MESH and DeCS descriptors. A total of 35 studies were selected, with eight (22.8%) reporting self-medication for COVID-19 prevention/treatment ranging from 14-83%, four (11.4%) reporting self-medication for specific symptoms ranging from 11-95%, 19 (54.4%) reporting several reasons for students self-medicating with a range of 50-100%, and four (11.4%) studies not specifying the reason for medication use in self-medication varying from 3-93%. The included studies revealed that the irrational use of medications is a common practice among university students, with varied prevalence of self-medication observed in this population during the COVID-19 pandemic.

Abstract Epilepsy affects around 50 million people worldwide, with 30% of them being refractory epilepsy. This shows that there is still a need for novel anti-seizure medication that have different mechanisms. One of the most common types of refractory epilepsy is temporal lobe epilepsy. Among the several effects of seizures on neurons is an increase in intracellular Ca2+ and activation of RhoA. Rapamycin is mTORC1 inhibitor, but long-term exposure to rapamycin (>18 hours) could also inhibit mTORC2. RhoA signaling pathway is regulated through the mTORC2 pathway; thus we hypothesized that long-term exposure to rapamycin could inhibit intracellular Ca2+ and RhoA activity as one of the mTORC2 downstream proteins, in a temporal lobe epilepsy model. This study used organotypic hippocampal slice cultures (OHSC) which were exposed to 20 nM rapamycin treatment for 3, 5, 8, and 10 days after induction of epilepsy by 7 μM kainic acid administration for 48 hours. Intracellular calcium concentration was observed using CLSM and RhoA activity with western blot. The results obtained from this research were long-term administration of rapamycin can decrease intracellular calcium concentration and RhoA activity in OHSC models of epilepsy induced by kainic acid, with the most effective duration is 5 days of exposure to rapamycin.

Abstract In this work, a methodology was developed to obtain dietary fiber from agro-industrial fruit and vegetable waste. The resulting raw material was named DF. The physicochemical analysis revealed a high total dietary fiber content, along with an appropriate soluble to insoluble fiber ratio and excellent water and fat retention capacity. Subsequently, its potential protective effect against hepatotoxicity induced by valproic acid (VPA) was investigated in Wistar rats, both as preventive and curative treatments. For this purpose, two different trials were conducted. In the preventive trial, VPA (250 mg/kg/day; oral) was administered concomitantly with DF (0.3 and 0.15 mg/kg/day) for 14 days. In the curative trial, VPA was administered for 14 days, followed by DF for an additional 14 days. The results demonstrated that DF supplementation normalized body weight, liver biomarkers and attenuated VPA-induced tissue damage, while normal liver architecture was preserved. These findings suggest that DF obtained from agro-industrial fruit and vegetable waste materials may serve as a functional feedstock to counteract the harmful effects associated with prolonged VPA treatment.

Abstract Collagen, the predominant protein in various organisms, is pivotal for tissue structure and mechanical properties. It has been extensively studied for its cosmetic, surgical, and anti-ageing applications, reflecting a growing interest in collagen-based cosmetics in Romania and prompting further research in this area. The study aimed to assess collagen’s efficacy and safety in dermocosmetology, comparing collagen peptides’ effectiveness in oral and topical applications. An analysis of the published studies on the subject was carried out, comparing the effectiveness of using collagen in different ways to improve skin conditions. The investigation included a literature review on collagen’s role in enhancing skin properties, covering its discovery, structure, chemical composition, systemic and topical applications, diverse sources, and skin penetration mechanisms. Hydrolysed collagen and its antioxidant properties are considered. The methods of investigating and monitoring the safety of cosmetic preparations are described. It has been concluded that topical collagen, similarly to nutraceutical supplements with collagen peptides, can slow down and reduce the signs of skin ageing and can increase skin elasticity, density, and moisture in equal measure. Studies have confirmed the harmlessness of collagen beyond doubt, but further investigation is necessary to determine the effectiveness of using different types of collagen.

Abstract Antimicrobial drug resistance is a challenge to public health. Various microorganisms, including methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, carbapenemase-producing Klebsiella pneumoniae, Pythium insidiosum, and Candida auris, have developed resistance to commonly used antimicrobials in infection disease treatments. Consequently, there is an urgent need to explore and develop novel therapeutic drugs. Natural products, particularly medicinal plants, have received attention in the quest for innovative treatments for various diseases. Plantago major is a plant endowed with several biological properties, such as antibacterial, antifungal, and healing actions. This study aimed to investigate the antimicrobial activities of the methanolic extract obtained from the leaves of P. major. Microdilution assays were conducted to determine the minimum inhibitory concentration and minimum bactericidal and fungicidal concentration. Additionally, synergism with antimicrobial drugs was assessed using a time-kill curve analysis. A synergistic bactericidal interaction between the extract and imipenem was observed against carbapenemase-producing K. pneumoniae. For MRSA, a bacteriostatic synergism was noted in combinations of the extract with cephalotin and oxacillin. For C. auris, a fungistatic interaction was observed between the extract and amphotericin B. These results suggest the presence of bioactive compounds within the extract with therapeutic potential for combating infections caused by these microorganisms.

Abstract Pathogenic strains of Escherichia coli can cause gastrointestinal infections, urinary tract infections (UTIs), bacteremia, and other severe infections. Some isolates of this species are capable of producing extended-spectrum β-lactamase (ESBL) enzymes, which mediate resistance against penicillin derivates and cephalosporins. Fungi of the Ascomycota phylum are known to produce antibiotics from different classes with activity against various bacterial agents. Among them, the genera Penicillium, Cephalosporium, Acremonium and Fusidium are known for the production of antimicrobial substances such as penicillin derivates, cephalosporins and fusidic acid. Currently, the search for new antimicrobials produced by species of the Ascomycota phylum includes the assessment of less explored habitats including aquatic environments, extreme environments, and the interior of plants/animals. The genus Penicillium remains promising for the discovery of new antimicrobial substances against resistant bacteria. In addition, those fungi have also been investigated regarding their usefulness for the biosynthesis of nanoparticles with antimicrobial activity. This narrative review introduces clinically relevant Escherichia coli pathovars, the historical contributions of the phylum Ascomycota to the production of antimicrobials, aspects of bioprocesses in the production of antimicrobial metabolites and different approaches of research targeting new antimicrobials such as screenings for fungi in environments not yet studied and the green synthesis mediated by fungi with antimicrobial activity.

Abstract Tagetes minuta L. is a naturalized species that is not endemic to the high-altitude fields of Santa Catarina in southern Brazil. In this study, we investigated the composition of the essential oil (EO) from the flowers of the plant and its larvicidal activity against Aedes aegypti. The EO was obtained by hydrodistillation using a Clevenger apparatus. The chemical composition was determined using gas chromatography coupled with mass spectrometry (GC-MS). The EO extraction yield was 4.9%, and the major compounds (Z)-tagetone, (Z)-β-ocimene, and dihydrotagetone were identified. The 24 h larvicidal activity was verified against that of L3 larvae of the Rockefeller strain of Ae. Aegypti. The EO showed larvicidal activity against Ae. aegypti, with LC50 = 17.28 μg/mL-1. The results indicate that the bioinsecticidal potential of T. minuta EO is promising for the development of research in the field of natural products.

Abstract The increasing interest in bioactive peptides (BPs) for their potential in disease control and health promotion has been accompanied by a lack of scalable processes for their purification, hindering their commercial production. Membrane filtration, especially using polymeric membranes (PMs), has emerged as a promising technique for BP separation due to its excellent separation performance, ease of fabrication, and flexibility. By utilizing natural sources, such as chitosan, cellulose, lignin, gelatin, alginate, keratin, and silk fibroin, in PM production, the environmental impact of membrane-based separation processes can be reduced while maintaining sustainable, eco-friendly approaches. Natural polymer membranes have exhibited excellent separation performance in terms of molecular weight cut-off and rejection of unwanted compounds, and their performance can be further improved by combining them with nanoparticles or other polymers. This review presents the recent updates on the use of PMs derived from natural sources for the separation of BPs, covering the production and functions of BPs, different membrane separation technologies, and challenges faced during downstream purification.

Abstract Metformin hydrochloride (MTF) has pharmacological properties for managing inflammatory skin conditions. MTF is a hydrophilic medication. Accordingly, embedding MTF into lipid carriers for enhancing skin penetration presents a challenge. The study aims to optimize the loading of MTF into nanostructured lipid carriers (NLCs) using a 22 full factorial design, employing the solvent injection technique. The NLCs were evaluated for encapsulation efficiency, hydrodynamic diameter, zeta potential, and polydispersity index. Alkalinization of the aqueous phase (pH = 12.5) resulted in maximizing the entrapment of MTF within NLCs. Furthermore, the tested solid lipids impacted the encapsulation of MTF based on their hydrophilic-lipophilic balance. The optimized formulation is composed of a lipid phase incorporating beeswax (75 mg), oleic acid (25 mg), and Span 60 (1% w/w), and an aqueous phase comprised of 1% w/w Tween 80, pH 12.5. The selected formula attained an entrapment efficiency of 53.68 ± 0.27%, a particle size of 333.0 ± 6.4 nm, and a negative surface charge, indicating adequate particles` stability. DSC and Molecular docking analyses confirmed the MTF incorporation within the lipid phase. The outcomes emphasize the importance of optimizing investigations in developing a viable delivery system for MTF to boost its permeation across the skin layers.

Abstract Sjögren’s syndrome (SS) damages exocrine glands, and Lilium brownii var. viridulum Baker (Lilii Bulbus, LB) shows potential as a therapeutic agent. This study evaluated LB’s efficacy in alleviating xerostomia using non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and human salivary gland acinar (NS-SV-AC) cells. In vitro, NS-SV-AC cells were treated with LB (1, 5, 10, 50, and 100 µg/mL) and 5-aza-2′-deoxycytidine (2 µM/mL) for 48 h. Cell viability, fluid secretion, and aquaporin-5 (AQP-5) expression were assessed. In vivo, thirty 20-week-old NOD/SCID mice received LB orally (100, 500, and 1,000 mg/kg) for 4 weeks, with salivary secretion rates measured. AQP-5 and M3 muscarinic acetylcholine receptor (M3R) expression and inflammatory mediator levels were determined using western blotting and enzyme-linked immunosorbent assay. Histopathological examination of salivary glands was also performed. LB significantly increased NS-SV-AC cell proliferation, fluid secretion, and AQP-5 expression. In NOD/SCID mice, LB reduced anti-SSA/Ro and anti-SSB/La antibodies, tumor necrosis factor-α, interferon-γ, and interleukin-6, while increasing AQP-5 and M3R expression. This resulted in increased salivary secretion and reduced glandular inflammation. LB extract appears promising for managing oral health by enhancing salivation, upregulating AQP-5, and modulating immune-inflammatory responses.

Abstract This research aims to create dabrafenib (DBF)-loaded nanosponges (NSPs) using β-cyclodextrin (β-CD) and diphenyl carbonate (DPC) as linker to improve oral bioavailability. DBF-loaded β-CD NSPs were synthesized by finely adjusting the molar ratio of β-CD to DPC and optimizing the stirring rate and duration using design methodology. After being loaded with DBF, the produced β-CD NSPs were characterized in terms of particle size, zeta potential (Z.P), polydispersity index (PdI), and drug entrapment efficiency (E.E). Studies on compatibility were carried out with FTIR (Fourier Transform Infrared Spectroscopy) and DSC (Differential Scanning Calorimetry). Permeability, in vivo, and in vitro experiments were performed on the improved NSPs and the pure medication. After optimizing DBF-loaded β-CD NSPs, a formulation with a mean size of 158.0 ± 7.2 nm, PdI of 0.282 ± 0.0044, and E.E of 86.23 ± 2.45% was obtained, based on the assessments indicated earlier. Zeta sizer, SEM, spectrum analysis, in vitro release, and pharmacokinetic tests were among the other analyses that further validated the optimization. An area under the curve (AUC0-t) of 7.95-fold greater and a Cmax 7.356 times higher than those of the free drug was demonstrated by the optimized β-CD NSPs, which showed a notable boost. The use of DBF-loaded NSPs holds promise as an effective strategy for enhancing release and bioavailability in the treatment of melanoma.

Abstract The study aimed to assess the prevalence and characteristics of potential drug-drug interactions (pDDIs) that increase the risk of QT prolongation, in a population of cardiovascular disease patients. An observational retrospective study was conducted at a cardiology ward. A total of 351 patients were included in the analysis, with almost equal gender distribution (female 48.4%) and mean age 70±10 years. In the total set of tested drug pairs (5620), QT-prolonging pDDIs were identified in 13 drug pairs on admission. The highest frequency was observed for ciprofloxacin (involved in 5 pDDIs), followed by propafenone (4 pDDIs) and beta2-agonists (4 pDDIs). The pharmacodynamic mechanism was involved in all pDDIs. The study revealed a low prevalence of QT-prolonging pDDIs on admission to the cardiology ward, about 3% in the studied population. However, given that underlying heart disease is a significant risk factor for the occurrence of QTc prolongation, the additional risk for acquired QT prolongation should not be neglected. Due to serious consequences caused by QT prolongation and TdP, the key role of health professionals is to identify predisposed patients and to recognize pDDIs involving QT-prolonging agents. Hence, patients’ modifiable risk factors for QT prolongation should be minimized, if not eliminated.

Abstract The transdermal pathway serves as a significant route for achieving localized or systemic effects. Within this context, the stratum corneum is a crucial barrier limiting the permeation of many drugs. To surmount this barrier, carriers, and nanocarriers have been utilised, notably ‘invasome’ being one such example. In our study, we formulated invasomes loaded with simvastatin using the conventional thin-layer evaporation technique. This formulation involved the use of soy phosphatidylcholine, terpene (Limonene), chloroform, and ethanol. Simvastatin-loadedinvasomes were incorporated into a carbopol 934 solution to create a gel. We prepared and assessed different formulationsfor various parameters, including zeta potential, scanning electron microscopy, entrapment efficiency, viscosity, and drug content, and conducted in vitro studies. The entrapment efficiency was as high as 83.17±0.61%. The maximum in vitro drug permeation (45.44±0.4%) was found in the gel with 0.5% soy phosphatidylcholine and 0.25% terpene. Upon evaluating these parameters, our findings suggest that the simvastatin invasomal gel effectively enhances drug permeability across membranes and successfully achieves prolonged drug release.