rss_2.0Acta Pharmaceutica FeedSciendo RSS Feed for Acta Pharmaceutica Pharmaceutica Feed effects of pravastatin and rosuvastatin on carbohydrate metabolism in an experimental diabetic rat model<abstract><title style='display:none'>Abstract</title> <p>Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg<sup>−1 </sup>day<sup>−1</sup> doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg<sup>−1 </sup>day<sup>−1</sup> reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg<sup>−1 </sup>day<sup>−1</sup>, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg<sup>−1 </sup>day<sup>−1</sup>, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg<sup>−1 </sup>day<sup>−1</sup>, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg<sup>−1 </sup>day<sup>−1 </sup>dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg<sup>−1 </sup>day<sup>−1</sup> is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.</p> </abstract>ARTICLEtrue comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality<abstract><title style='display:none'>Abstract</title> <p>The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.</p> </abstract>ARTICLEtrue compounds isolated from potentiate irinotecan anticancer activity against colorectal cancer cells<abstract><title style='display:none'>Abstract</title> <p>Although the anticancer activity of <italic>Dorstenia foetida</italic> was already observed, the chemical entity responsible for this activity remained unidentified. In this study, the cytotoxic activity of two furanocoumarin compounds, <italic>i</italic>.<italic>e</italic>., 5-methoxy--3-(3-methyl-2,3-dihydroxybutyl)-psoralen (<bold>1</bold>) and 5-methoxy-3-(3-methyl-2,3-dihydroxybutyl)-psoralen diacetate (<bold>2</bold>) isolated from ethyl acetate fraction of <italic>D. foetida </italic>(whole plant) was investigated in several cancer cell lines including HN22, MDA-MB-231, HCT116, and HT29. The results revealed that compound <bold>2</bold> exhibited cytotoxic activity, particularly against colorectal cancer cell lines HCT116 and HT29. The interplay between compound <bold>2</bold> and irinotecan (Iri) showed synergism against HCT116, which was analyzed by CompuSyn software. The simulation revealed that, at the molar ratio of Iri:<bold>2</bold> of 1:40, the concentration predicted to achieve a 90 % inhibitory effect when used in the combination would be ~28- and ~4-fold lower than the concentration of compound <bold>2</bold> and Iri, resp., when used individually. Finally, the percentage of apoptotic cells in the HCT116 line treated with the combination was markedly higher than in the cells treated with the individual agent (60 % apoptotic cells for the combination compared to 17 and 45 % for Iri and compound <bold>2</bold> monotherapy, resp). In conclusion, our results identified compound <bold>2 </bold>as a plant-derived compound exhibiting anticancer properties that can act synergistically with Iri and warranted further research to assess the potential of this synergism for colorectal cancer treatment.</p> </abstract>ARTICLEtrue composition and potential antioxidant, anti-inflammatory, and analgesic efficacy of L.<abstract><title style='display:none'>Abstract</title> <p>This study aims to assess the chemical composition of the aqueous extract of <italic>Cistus albidus</italic> L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in <italic>C. albidus</italic> seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect <italic>in vivo</italic>, and albumin denaturation to evaluate the anti-inflammatory effect <italic>in vitro</italic>. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy <italic>in vivo</italic>.</p> <p>Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg<sup>−1</sup>), quercitrin (1,235.8 mg kg–1) and gallic acid (628. 2 mg kg<sup>−1</sup>). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of <italic>C. albidus</italic>. The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proantho cyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL<sup>−1</sup> for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that <italic>C. albidus</italic> extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant.</p> </abstract>ARTICLEtrue of mineral composition of leaves and flowers of wild-growing<abstract><title style='display:none'>Abstract</title> <p>The objective of this study was to determine the mineral content in the leaves and flowers of wild-grown <italic>Sambucus nigra</italic> collected from eleven different locations in Kosovo. The samples were digested in a microwave system using the wet digestion method. The minerals were determined by the application of inductively coupled plasma-atomic emission spectrometry (ICP-AES) and inductively coupled plasma-mass spectrometry (ICP-MS). A total of 31 elements were determined, 15 elements by the ICP-AES method (Al, B, Ba, Ca, Cr, Cu, Fe, K, Mg, Mn, Na, P, Sr, V, and Zn) and 16 elements by the ICP-MS method (Ag, As, Be, Bi, Cd, Co, Cs, Ga, Hg, In, Li, Ni, Pb, Rb, Tl, and U). The leaves of <italic>S. nigra</italic> show a higher content of minerals compared to the flowers, except for the flower of the sample SN-FL10, which is characterized by a high concentration of Fe, Al, Pb, Be, and Tl. The concentration of heavy metals and toxic elements (Pb, Cd, and Hg) was within the permissible concentrations according to Eur. Ph.</p> </abstract>ARTICLEtrue inhibits the proliferation of human multiple myeloma cells by inducing apoptosis and G2/M cell cycle arrest: Involvement of Akt and p38 MAPK signalling pathway<abstract><title style='display:none'>Abstract</title> <p>Deguelin exhibits antiproliferative activity against various cancer cell types. Previous studies have reported that deguelin exhibits pro-apoptotic activity against human cancer cells. The current study aimed at further elaborating the anticancer effects of deguelin against multiple myeloma cells. Cell growth estimations were made through MTT assay. Phase contrast microscopy was used for the analysis of the viability of multiple myeloma cells. Colony formation from multiple myeloma cells was studied using a clonogenic assay. Antioxidative assays for determining levels of glutathione (GSH) and superoxide dismutase (SOD) were carried out after treating multiple myeloma cells with deguelin. The apoptosis of multiple myeloma cells was studied using AO/EB and Annexin V-FITC/PI staining methods. Multiple myeloma cell cycle analysis was performed through flow cytometry. mRNA expression levels were depicted using qRT-PCR. Migration and invasion of multiple myeloma cells were determined with the wound-healing and transwell assays, respectively. Deguelin specifically inhibited the multiple myeloma cell growth while the normal plasma cells were minimally affected. Multiple myeloma cells when treated with deguelin exhibited remarkably lower viability and colony-forming ability. Multiple myeloma cells treated with deguelin produced more SOD and had higher GSH levels. The multiple myeloma cell growth, migration, and invasion were significantly declined by <italic>in vitro</italic> administration of deguelin. In conclusion, deguelin treatment, when applied <italic>in vitro,</italic> induced apoptotic cell death and resulted in mitotic cessation at the G2/M phase through modulation of cell cycle regulatory mRNAs in multiple myeloma cells.</p> </abstract>ARTICLEtrue suppresses lung cancer cell growth and by inducing cell apoptosis<abstract><title style='display:none'>Abstract</title> <p>Lung cancer (LC) is the leading cause of cancer deaths worldwide. Surgery, chemoradiotherapy, targeted therapy, and immunotherapy are considered dominant treatment strategies for LC in the clinic. However, drug resistance and meta-stasis are two major challenges in cancer therapies. Medicarpin (MED) is an isoflavone compound isolated from alfalfa, which is usually used in traditional medicine. This study was de sig ned to evaluate the anti-LC effect and reveal the underlying mechanisms of MED <italic>in vivo</italic> and <italic>in vitro</italic>. We found that MED could significantly inhibit proliferation, induce apoptosis, and cell cycle arrest of A549 and H157 cell lines. Basically, MED induced cell apoptosis of LC cells by upregu lating the expression of pro-apoptotic proteins BAX and Bak1, leading to the cleavage of caspase-3 (Casp3). Moreover, MED inhibited the proliferation of LC cells <italic>via</italic> downregulating the expression of proliferative protein Bid. Overall, MED inhibited LC cell growth <italic>in vitro</italic> and <italic>in vivo via</italic> suppressing cell proliferation and inducing cell apoptosis, suggesting the therapeutic potential of MED in treating LC.</p> </abstract>ARTICLEtrue (±)---lactam ureas: Synthesis, and biological profiling<abstract><title style='display:none'>Abstract</title> <p>A diastereomeric mixture of racemic 3-phthalimido-<italic>b</italic>-lactam <bold>2a</bold>/<bold>2b</bold> was synthesized by the Staudinger reaction of carboxylic acid activated with 2-chloro-1-methylpyridinium iodide and imine <bold>1</bold>. The amino group at the C3 position of the <italic>b</italic>-lactam ring was used for further structural upgrade. <italic>trans</italic>-<italic>b</italic>-lactam ureas <bold>4a–t</bold> were prepared by the condensation reaction of the amino group of <italic>b</italic>-lactam ring with various aromatic and aliphatic isocyanates. Antimicrobial activity of compounds <bold>4a–t</bold> was evaluated <italic>in vitro </italic>and neither antibacterial nor antifungal activity were observed. Several of the newly synthesized <italic>trans</italic>-<italic>b</italic>-lactam ureas <bold>4a–c</bold>, <bold>4f</bold>, <bold>4h</bold>, <bold>4n</bold>, <bold>4o</bold>, <bold>4p</bold>, and <bold>4s</bold> were evaluated for <italic>in vitro</italic> antiproliferative activity against liver hepatocellular carcinoma (HepG2), ovarian carcinoma (A2780), breast adenocarcinoma (MCF7) and untransformed human fibroblasts (HFF1). The <italic>b</italic>-lactam urea <bold>4o</bold> showed the most potent antiproliferative activity against the ovarian carcinoma (A2780) cell line. Compounds <bold>4o</bold> and <bold>4p</bold> exhibited strong cytotoxic effects against human non-tumor cell line HFF1. The <italic>b</italic>-lactam ureas <bold>4a–t</bold> were estimated to be soluble and membrane permeable, moderately lipophilic molecules (log<italic>P</italic> 4.6) with a predisposition to be CYP3A4 and P-glycoprotein substrates. The tools PASS and SwissTargetPrediction could not predict biological targets for compounds <bold>4a–t</bold> with high probability, pointing to the novelty of their structure. Considering low toxicity risk, molecules <bold>4a</bold> and <bold>4f</bold> can be selected as the most promising candidates for further structure modifications.</p> </abstract>ARTICLEtrue non-coding RNA suppresses growth and epithelial-mesenchymal transition by inhibiting Wnt/-catenin signaling pathway in human pancreatic cancer PANC-1 cells: Insights from and studies<abstract><title style='display:none'>Abstract</title> <p>There is increasing evidence that long non-coding RNAs (lncRNAs) play a crucial role in the development and progression of malignant tumors, particularly pancreatic cancer. In this study, the influence of the lncRNA <italic>TINCR</italic> on the behavior of human pancreatic cancer cells was investigated with the aim of deciphering its role in growth, migration, and invasion. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to investigate <italic>TINCR</italic> expression in pancreatic cancer cells. Ectopic expression of <italic>TINCR</italic> in PANC-1 cells was induced to evaluate the effects on cell viability and apoptosis, examining the apoptotic genes Bax and Bcl-2. Migration and invasion assays were used to measure the impact of <italic>TINCR</italic> on these cellular processes. <italic>In vivo</italic> studies using a xenograft mouse model examined the effects of <italic>TINCR</italic> on tumor growth, epithelial-to-mesenchymal transition (EMT) markers, and the Wnt/β-catenin signaling pathway. PANC-1 cells showed strikingly low <italic>TINCR</italic> expression compared to other pancreatic cancer cell lines. Ectopic <italic>TINCR</italic> expression reduced the viability of PANC-1 cells primarily by inducing apoptosis, as evidenced by increased Bax and decreased Bcl-2 expression. Overexpression of <italic>TINCR</italic> significantly increased the percentage of apoptotic cells. It also decreased the migration and invasion ability of PANC-1 cells, as demonstrated in wound healing and transwell assays. In addition, overexpression of <italic>TINCR</italic>-suppressed proteins is associated with the Wnt/β-catenin signaling pathway in PANC-1 cells. In the xenograft mouse model, overexpression of <italic>TINCR</italic> inhibited tumor growth, EMT markers, and proteins associated with the Wnt/β-catenin pathway. This study sheds light on the tumour-suppressive role of <italic>TINCR</italic> in PANC-1 cells and suggests its potential as a therapeutic target. These results shed light on the molecular mechanisms underlying the impact of <italic>TINCR</italic> on pancreatic cancer and offer promising opportunities for innovative therapeutic strategies to improve outcomes in this serious malignancy.</p> </abstract>ARTICLEtrue liposomal hydrogel: a step forward for enhanced treatment of MRSA-related skin infections<abstract> <title style='display:none'>Abstract</title> <p>Azithromycin (AZT) encapsulated into various types of liposomes (AZT-liposomes) displayed pronounced <italic>in vitro</italic> activity against methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA) (1). The present study represents a follow-up to this previous work, attempting to further explore the anti-MRSA potential of AZT-liposomes when incorporated into chitosan hydrogel (CHG). Incorporation of AZT-liposomes into CHG (liposomal CHGs) was intended to ensure proper viscosity and texture properties of the formulation, modification of antibiotic release, and enhanced antibacterial activity, aiming to upgrade the therapeutical potential of AZT-liposomes in localized treatment of MRSA-related skin infections. Four different liposomal CHGs were evaluated and compared on the grounds of antibacterial activity against MRSA, AZT release profiles, cytotoxicity, as well as texture, and rheological properties. To our knowledge, this study is the first to investigate the potential of liposomal CHGs for the topical localized treatment of MRSA-related skin infections. CHG ensured proper viscoelastic and texture properties to achieve prolonged retention and prolonged release of AZT at the application site, which resulted in a boosted anti-MRSA effect of the entrapped AZT-liposomes. With respect to anti-MRSA activity and biocompatibility, formulation CATL-CHG (cationic liposomes in CHG) is considered to be the most promising formulation for the treatment of MRSA-related skin infections.</p> </abstract>ARTICLEtrue impact of cryoprotectant exposure time on post-thaw viability of autologous and allogeneic hematopoietic stem cells and leukocyte subpopulations<abstract> <title style='display:none'>Abstract</title> <p>Although the use of cryoprotectant dimethyl sulfoxide (DMSO) is the gold standard in cryopreservation of hematopoietic stem cells, it is well known that it has a negative effect on cell viability. The aim of this prospective study was to examine how the length of post-thaw exposure to DMSO affects the cell viability and stability of peripheral blood stem cell (PBSC) samples. Additionally, the effects of donor type and pre-cryopreservation storage time on post-thaw viability during the stability study were evaluated. In 30 autologous and 30 allogeneic PBSC samples viable CD34+, CD14+, CD19+, CD16+/56+, and CD3+ cells were determined immediately after thawing, and one-and three-hours post-thaw.</p> <p>Analysis of the absolute count of viable cells in thawed samples showed a significant difference between all measurement points for CD34+ (<italic>p</italic> &lt; 0.001), CD14+ (<italic>p</italic> &lt; 0.001), and CD19+ cells (<italic>p</italic> &lt; 0.001). No significant differences were observed for post-thaw stability of allogeneic samples analysed between products stored before cryopreservation ≥ 24 hours (N = 20), and those stored &lt; 24 hours (N = 10), except for viable CD3+/CD4+ cells after three hours post-thaw (<italic>p</italic> = 0.028). In conclusion, DMSO had different effects on leukocyte subpopulations in cryopre-served PBSC samples. The type of donors and the length of storage before cryopreservation did not affect the post-thaw stability of cryopreserved PBSC samples.</p> </abstract>ARTICLEtrue about medicines’ association with endocrine therapy adherence in early breast cancer survivors in Croatia<abstract> <title style='display:none'>Abstract</title> <p>This observational, cross-sectional study conducted at the University Hospital Centre Zagreb (UHC Zagreb) aimed to explore patients’ beliefs about adjuvant endocrine therapy (AET) as well as their association with non-adherence and sociodemographic and clinical factors. Out of 420 early breast cancer (BC) patients included in the study, 79.5 % perceived AET necessary and important for their health, as measured by the Belief About Medicines Questionnaire (BMQ), with the mean necessity score (20.4 ± 3.68) significantly higher than the mean concerns score (13 ± 4.81) (<italic>p</italic> &lt; 0.001). Based on the Medication Adherence Report Scale (MARS-5), 44.4 % (<italic>n</italic> = 182) of the participants were non-adherers, out of which 63.2 % (<italic>n</italic> = 115) were unintentional and 36.8 % (<italic>n</italic> = 67) intentional non-adherers. Significantly higher concern beliefs were found among patients that were younger (<italic>p</italic> &lt; 0.001), employed (<italic>p</italic> &lt; 0.001), intentionally non-adherent to AET (<italic>p</italic> = 0.006), had a lower body-mass index (<italic>p</italic> = 0.005) and a higher level of education (<italic>p</italic> &lt; 0.001), were premenopausal at the time of diagnosis (<italic>p</italic> &lt; 0.001), taking tamoxifen treatment (<italic>p</italic> = 0.05) and receiving ovarian suppression (<italic>p</italic> &lt; 0.001). Younger patients should be recognized as being at risk of non-adherence as they hold greater concern beliefs about medicines.</p> </abstract>ARTICLEtrue’s discovery of the periodic table and the first European Academy of Sciences to honour him<abstract> <title style='display:none'>Abstract</title> <p>The chemical science community will commemorate the 155<sup>th</sup> anniversary of Mendeleev’s groundbreaking discovery of the periodic table of elements in 2024. This paper aims to underscore the significance of Mendeleev’s honorary membership in the Academy of Sciences in Zagreb, Croatia, which occurred in 1882, making it the first scientific academy in Europe to extend this recognition. Additionally, we seek to explore the contextual circumstances that contributed to this noteworthy event within the broader European context. To provide insight into the specificities and variations in the influence and reception of the periodic table of elements within the educational process of select European countries (Russia, Germany, Czech Lands, Serbia), we conducted a comprehensive review, drawing comparisons to Croatia. Notably, upon its initial publication in 1869, the discovery of the periodic table did not gain immediate acceptance in Croatia, largely attributed to the absence of a well-established presence of chemical science within the country. About fifteen years passed from Mendeleev’s discovery of the periodic law to its reception and dissemination throughout Croatia. Despite an initial delay, Croatian chemical science followed the development of the periodic table through secondary and university education, while actively partaking it in.</p> </abstract>ARTICLEtrue’ approval rate of pharmacist-initiated interventions to optimise patients’ clinical status of hypertension in the ambulatory care setting<abstract> <title style='display:none'>Abstract</title> <p>This perspective, pre- and post-intervention study with a one-year follow-up primarily aimed to ascertain prescribers’ approval rate of pharmacists’ interventions and clinical status of hypertension following comprehensive medication management (CMM) intervention in the ambulatory care clinic. Between January 2018 and January 2022 overall 100 patients with hypertension and other comorbidities were referred to the CMM services at the Health Centre Zagreb – Centar (HCZC). Out of 275 interventions directed to prescribers, 73.1 % of interventions were approved, 12.4 % were rejected and 14.5 % were not reviewed. The percentage of patients with a blood pressure goal increased from 45 % at the initial consultation to 82.5 % at the patients’ latest encounter (<italic>p</italic> &lt; 0.001). The average number of drug therapy problems (DTPs) per patient totaled 3.53 ± 1.80, where 98 % of patients had one or more DTPs, 48 % had 4 or more DTPs, whereas 26 % had 5 or more DTPs. Sub-therapeutic dosage (32.6 %) and the need for additional drug therapy (30.9 %) were the two most commonly identified DTPs. These results reinforce the need to integrate pharmacy-led services in the primary care setting with the aim of improving patients’ health outcomes.</p> </abstract>ARTICLEtrue of astaxanthin/zeaxanthin-loaded nanostructured lipid carriers for enhanced bioavailability: Characterization-, stability-and permeability study<abstract> <title style='display:none'>Abstract</title> <p>Astaxanthin (ASTA) and zeaxanthin (ZEA) are xanthophyll carotenoids showing a wide spectrum of health-promoting properties. However, their utilization is limited, mostly due to poor water solubility, limited bioavailability, and a tendency to oxidate, as well as photo- and thermal instability. The aim of this work was to develop ASTA- and ZEA-loaded nano-structured lipid carriers (NLCs) that would protect them against degradation and improve their intestinal stability/permeability. Obtained NLCs were characterized by an effective diameter of 294 nm for ASTA-NLC and 280 nm for ZEA-NLC; polydispersity index (<italic>PDI</italic>) lower than 0.2; and zeta potential of –29.4 mV and –29.0 mV, respectively. Interestingly, despite similar physicochemical characteristics, our investigation revealed differences in the encapsulation efficiency of ASTA-NLC and ZEA-NLC (58.0 % <italic>vs</italic>. 75.5 %, respectively). Obtained NLCs were stable during a 21 day-storage period in the dark at room temperature or at 4 °C. Investigation of gastrointestinal stability showed no change in effective diameter and <italic>PDI</italic> under gastric conditions while both parameters significantly changed under intestinal conditions. Our results showed for the first time that both ASTA- and ZEA-NLCs intestinal absorption investigated in the <italic>in vitro</italic> model is significantly increased (in relation to pure compounds) and is affected by the presence of mucus. This study provides useful data about the advantages of using NLC as a delivery system for ASTA and ZEA that might facilitate their applications in the food and pharmaceutical industry.</p> </abstract>ARTICLEtrue, antiproliferative and antiplasmodial evaluation of new chloroquine and mefloquine-based harmiquins<abstract> <title style='display:none'>Abstract</title> <p>Here we present the synthesis and evaluation of the biological activity of new hybrid compounds, ureido-type (UT) harmiquins, based on chloroquine (CQ) or mefloquine (MQ) scaffolds and β-carboline alkaloid harmine against cancer cell lines and <italic>Plasmodium falciparum</italic>. The hybrids were prepared from the corresponding amines by 1,1′-carbonyldiimidazole (CDI)-mediated synthesis. <italic>In vitro</italic> evaluation of the biological activity of the title compounds revealed two hit compounds. Testing of the antiproliferative activity of the new UT harmiquins, and previously prepared triazole-(TT) and amide-type (AT) CQ-based harmiquins, against a panel of human cell lines, revealed TT harmiquine <bold>16</bold> as the most promising compound, as it showed pronounced and selective activity against the tumor cell line HepG2 (<italic>IC</italic><sub>50</sub> = 5.48 ± 3.35 μmol L<sup>−1</sup>). Screening of the antiplasmodial activities of UT harmiquins against erythrocytic stages of the <italic>Plasmodium</italic> life cycle identified CQ-based UT harmiquine <bold>12</bold> as a novel antiplasmodial hit because it displayed low <italic>IC</italic><sub>50</sub> values in the submicromolar range against CQ-sensitive and resistant strains (<italic>IC</italic><sub>50</sub> 0.06 ± 0.01, and 0.19 ± 0.02 μmol L<sup>−1</sup>, respectively), and exhibited high selectivity against <italic>Plasmodium</italic>, compared to mammalian cells (SI = 92).</p> </abstract>ARTICLEtrue exclusion chromatography as green support for forced degradation study of adalimumab<abstract> <title style='display:none'>Abstract</title> <p>Size exclusion chromatography (SEC) has become a powerful tool for analysing size variants of biologic drugs in their native form. Modern SEC can be defined by the use of chromatographic columns packed with sub-3 µm particles, allowing an increase in method throughput compared to that of conventional SEC.</p> <p>We performed the forced degradation study of adalimumab, the first genetically engineered fully humanised immunoglobulin G1 monoclonal antibody, and evaluated tha possibilities of an advanced SEC column packed with sub-3 µm particles for elucidation of the degradation pathway. Our results revealed the main adalimumab degradation products to be antibody fragments. Acidic and basic conditions had the most intensive effect on the degradation of the adalimumab while the drug exhibits relative stability under thermal and photolytic stress conditions.</p> <p>The AGREE and AGREEprep calculators were used for the evaluation of the environmental performance of the forced degradation procedure. The results of the green score evaluation are presented as round pictograms with a circle in the centre that shows the overall score of 0.81 and 0.61, respectively. Both pictograms are highlighted in green, indicating the eco-friendly conditions.</p> </abstract>ARTICLEtrue adherence in patients with advanced breast cancer: focus on CDK4/6 inhibitors<abstract> <title style='display:none'>Abstract</title> <p>Treatment adherence is crucial for optimal outcomes in advanced breast cancer, but can be challenging due to various factors, <italic>i.e</italic>. patients’ attitudes and behavior upon diagnosis, and complex therapies with high adverse effect rates. Our aim was to explore the adherence to oral anticancer medications (OAM) in women with advanced breast cancer, focusing on cyclin-dependent kinase 4 and 6 inhibitors (CDKI), and identify factors associated with the adherence. We conducted a cross-sectional study at the University Hospital Centre Zagreb, Croatia, involving women with stage IV advanced breast cancer receiving OAM. Data collection included a questionnaire assessing socio-demographic and clinical information, Beck Depression Inventory-II for depressive symptoms, Medication Adherence Report Scale (MARS-5) for adherence to OAM, and Beliefs about Medicines Questionnaire. Plasma concentrations of CDKI were confirmed by LC-MS/MS in three randomly selected participants. A total of 89 women were included. The most prescribed OAMs were anti-estrogen (71.3 %) and CDKI (60.9 %). MARS-5 scores (mean: 24.1 ± 1.6) correlated with CDKI plasma concentrations. Forgetfulness was the primary reason for non-adherence (25.9 %). Women receiving CDKI (<italic>p</italic> = 0.018), without depressive symptomatology (<italic>p</italic> = 0.043), and with more positive beliefs about medicines were more adherent (<italic>p</italic> &lt; 0.05). This study enhances understanding of medication adherence in advanced breast cancer and identifies influential factors.</p> </abstract>ARTICLEtrue in olive leaf, branch, and stem extracts: stability and biological activity in human cervical carcinoma and melanoma cells<abstract> <title style='display:none'>Abstract</title> <p>Olive leaves as a main byproduct of olive oil and fruit industry are a valuable source of phytochemicals such as polyphenols, with multiple biomedical effects. Apart from leaves, olive branches and stems make up a significant amount of olive waste. It is well known that the drying process and long-term storage affect the stability and concentration of polyphenols present in raw materials. For that matter, two different means of storing olive waste, at room temperature and +4 °C, were compared by determining the content of the polyphenol oleuropein (OLE) in olive leaf, branch, and stem extracts (LE, BE, and SE) by HPLC-DAD method. Total phenols (TPC), <italic>o</italic>-diphenols (<italic>o</italic>-DPC), and total flavonoids (TFC) content in extracts were assessed by UV-Vis measurements. LE prepared from leaves stored at +4 °C had the highest OLE content, 30.7 mg g<sup>−1</sup> of dry extract (DE). SE from stems stored at +4 °C was the richest in TPC and TFC (193 mg GAE/g DE and 82.9 mg CE/g DE, respectively), due to the higher purity of the extract. The biological activity of extracts was determined on cervical cancer (HeLa), melanoma (A375), metastatic melanoma (A375M) tumor cell lines, and on spontaneously immortalized cell line of keratinocytes (HaCaT), using the MTT assay. The data show that all extracts had a similar dose-dependent effect on cell viability in HeLa cells, while the effect of LE on melanoma A375 and A375M, and HaCaT cells was cell-line dependent.</p> </abstract>ARTICLEtrue determination of macrolides in water samples by solid-phase extraction and capillary electrophoresis<abstract> <title style='display:none'>Abstract</title> <p>Solid-phase extraction (SPE) coupled with capillary electrophoresis (CE) for the determination of macrolide antibiotics (azithromycin, clarithromycin, roxithromycin, tylosin) and tiamulin in water samples was described in this article. These compounds were extracted with different types of sorbents ( Oasis HLB, C18, C8, SDB, and Strata-X) and different masses of sorbents (60 mg, 200 mg, and 500 mg) using different organic solvents (methanol, ethanol, and acetonitrile) and different pH values of water samples (pH 7.00, 8.00, and 9.00). It was found that the highest extraction efficiency of the studied compounds was obtained with 200 mg/3 mL C18 cartridges with methanol as eluent at pH 9.00 of the water sample. The developed SPE-CE method for macrolide antibiotics and tiamulin was validated for linearity, precision, repeatability, the limit of detection (<italic>LOD</italic>), the limit of quantification (<italic>LOQ</italic>), and recovery. Good linearity was obtained in the range of 0.3–30 mg L<sup>−1</sup> depending on the drug, with correlation coefficients higher than 0.9958 in all cases except clarithromycin (0.9873). Expanded measurement uncertainties were calculated for each pharmaceutical, accounting for 20.31 % (azithromycin), 38.33 % (tiamulin), 28.95 % (clarithromycin), 26.99 % (roxithromycin), and 21.09 % (tiamulin). Uncertainties associated with precision and calibration curves contributed the most to the combined measurement uncertainty. The method was successfully applied to the analysis of production waste-water from the pharmaceutical industry.</p> </abstract>ARTICLEtrue