Acta Pharmaceutica最新文献

{"title":"Freeze-dried kit formulation and physicochemical assessment of a daratumumab-based radiopharmaceutical.","authors":"Paulina Apostolova, Marija Atanasova Lazareva, Katarina Davalieva, Marija Arev, Dino Karpicarov, Petre Makreski, Irena Slaveska Spirevska, Ivana Mitrevska, Aleksandar Dimovski, Sanja Vranješ-Đurić, Emilija Janevik-Ivanovska","doi":"10.2478/acph-2026-0013","DOIUrl":"10.2478/acph-2026-0013","url":null,"abstract":"<p><p>Daratumumab is a fully human anti-CD38 monoclonal antibody with strong potential as a targeting vector for therapeutic radionuclides. This study aimed to develop a freeze-dried daratumumab immunoconjugate kit by selecting a suitable chelator (DOTA-NHS, <i>p</i>-SCN-Bn-DOTA, or <i>p</i>-SCN-Bn-1B4M-DTPA) for the ¹⁷⁷Lu-labelling, optimising the freeze-drying formulation, and evaluating the physicochemical properties and purity profiles. Conjugation performed in carbonate buffer at elevated temperature enhanced chelator incorporation and supported the selection of daratumumab-<i>p</i>-SCN-Bn-DOTA as the most suitable candidate, achieving radiolabelling yield up to 99.8 % without additional purification. Among the evaluated freeze-dried formulations, a saline-based, buffer-free sucrose-mannitol formulation containing polysorbate 20 (S.F5) provided the most favourable characteristics, including minimal residual moisture and the highest monomer purity with non-detectable HMWS species under the applied SE-HPLC conditions. ATR-FTIR and Raman spectroscopy confirmed preservation of the antibody structural integrity after conjugation and freeze-drying. In an <i>in vitro</i> study using human serum, [¹⁷⁷Lu]Lu-daratumumab-<i>p</i>-SCNBn-DOTA maintained higher radiochemical purity for 168 h than [¹⁷⁷Lu]Lu-daratumumab-<i>p</i>-SCN-Bn-1B4MDTPA, indicating greater stability. These results support the feasibility of a ready-to-use freeze-dried daratumumab-<i>p</i>-SCN-Bn-DOTA kit for the ¹⁷⁷Lu-labelling.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-16"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electron paramagnetic resonance studies of free radicals: The research legacy of Janko N. Herak.","authors":"Erim Bešić, Valerije Vrček, Davor Šakić","doi":"10.2478/acph-2026-0014","DOIUrl":"10.2478/acph-2026-0014","url":null,"abstract":"<p><p>This review presents a chronological analysis of the scientific contributions of Professor Janko N. Herak (1937-2025), a Croatian biophysicist whose research played a major role in the development of electron para-magnetic resonance (EPR) spectroscopy in Croatia and significantly advanced the study of free radicals in biological systems. Beginning with his early work at Duke University under the mentorship of Prof. Walter Gordy, Herak investigated radiation-induced radicals in nucleic acid bases, nucleosides, and related biomolecules using EPR spectroscopy. During subsequent decades at the Ruđer Bošković Institute and later at the University of Zagreb Faculty of Pharmacy and Biochemistry, he conducted extensive studies of free radicals in irradiated single crystals of nucleic acid constituents, elucidating mechanisms of radical formation, hydrogen transfer, and structural rearrangements. His research later expanded to the investigation of oxidative processes in biological macromolecules, particularly the slow oxidation of plasma lipoproteins, where EPR spectroscopy and kinetic modelling provided insight into radical-mediated lipid peroxidation and the physicochemical basis of lipoprotein modification. In parallel, Herak explored long-range charge migration in nucleobase crystals and investigated metal-nucleobase interactions, integrating experimental EPR and ENDOR spectroscopy with theoretical modelling. These studies contributed to a deeper understanding of radical stabilisation, electronic structure, and energy transfer in ordered molecular systems. By situating Herak's work within the broader development of radiation chemistry and magnetic resonance spectroscopy, this review highlights the methodological rigour, conceptual contributions, and lasting scientific impact of his research on free radicals and biologically relevant molecular systems.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-22"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>β</i>-Carboline and chloroquine hybrids as potent antiplasmodial agents: Design, synthesis and biological evaluation.","authors":"Ana Penava, Lais Pessanha De Carvalho, Jana Held, Goran Poje, Zrinka Rajić, Ivana Perković","doi":"10.2478/acph-2026-0016","DOIUrl":"https://doi.org/10.2478/acph-2026-0016","url":null,"abstract":"<p><p>A series of thirteen novel <i>β</i>-carboline and chloroquine (CQ) hybrids was designed and synthesized. The compounds were evaluated for <i>in vitro</i> antiplasmodial activity against <i>Plasmodium falciparum</i> strains 3D7 (CQ-sensitive) and Dd2 (multidrug-resistant). All compounds exhibited potent activity, with <i>IC</i> ₅₀ values in the nanomolar to low micromolar range, while retaining potency against the resistant strain (1.0 to 365.5 nmol L^-1 for 3D7 and from 2.2 to 2415.3 nmol L^-1 for Dd2 strain). Several compounds were more active against Dd2, then against 3D7 strain with resistance index (RI) lower than 1. Moreover, nearly all compounds showed lower RI values compared to CQ which additionally underscores their outstanding activity. At the highest tested concentration (250 μmol L^-1), no cytotoxicity was observed in HepG2 cells, resulting in favourable selectivity indices expressed as lower limits. Overall, the obtained results confirm strong antiplasmodial activity of the <i>β</i>-carboline and chloroquine hybrids as promising antiplasmodial candidates, particularly due to their activity against resistant strains and improved selectivity.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-26"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pelargonidin protects retinal ganglion cells in a streptozotocin-induced diabetic rat model by reducing intraocular pressure, suppressing TGF-β and activating JAK2/STAT3 signalling pathway.","authors":"Haichun Yu, Ashraf Albrakati, Ejaz Akbar Wani, Ying Li","doi":"10.2478/acph-2026-0010","DOIUrl":"10.2478/acph-2026-0010","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is one of the primary causes of vision impairment, affecting individuals with diabetes, and is marked by the neurodegeneration of the retina along with increased intraocular pressure (IOP). This study sought to determine the effects of pelargonidin on extracellular matrix (ECM) modulation and the inhibition of transforming growth factor-β (TGF-β) and Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) pathway in retinal ganglion cells of streptozotocin-induced diabetic rats. Male Sprague-Dawley rats (180-200 g) were rendered diabetic by intraperitoneal administration of streptozotocin (STZ). The rats were divided into 5 groups: control, diabetic model (STZ), STZ + low dose pelargonidin (12.5 mg kg^-1 per day), STZ + medium dose pelargonidin (25 mg kg-1 per day) and STZ + high dose pelargonidin (50 mg kg^-1 per day). IOP was monitored using a tonometer. Whole-mount retinal immunofluorescence staining using RNA-binding protein with multiple splicing (RBPMS) was performed to assess retinal ganglion cell (RGC) density. Protein expression levels of apoptotic markers, ECM components, and TGF-β and JAK2/STAT3 signalling pathways were evaluated by Western blotting. Pelargonidin treatment dose-dependently reduced the elevated IOP. Importantly, immunofluorescence analysis revealed a marked dose-dependent preservation of retinal ganglion cell (RGC) density: STZ-induced RGC loss was significantly reversed by pelargonidin, with the highest dose restoring RGC density to near-control or higher levels in both the central and peripheral retina. This was achieved <i>via</i> modulation of apoptosis-related proteins through the upregulation of Bcl-xL, Bcl-2, and downregulation of Bad, Bax and cleaved caspase-3. Furthermore, pelargonidin modulated ECM remodelling protein expression in the RGC layer. In particular, TGF-β2/Smad2/3 signalling was downregulated, and the JAK2/STAT3 pathway was upregulated. By reducing IOP, preserving RGC density, modulating ECM deposition, inhibiting TGF-β and upregulating the JAK2/STAT3 pathway, pelargonidin exerts protective effects against diabetic retinal injury. The results of this study further confirm the pharmacological potential of pelargonidin as a therapeutic agent for diabetic retinopathy.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-15"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep eutectic solvents in pharmaceutical applications: A review.","authors":"Li Zechen","doi":"10.2478/acph-2026-0012","DOIUrl":"10.2478/acph-2026-0012","url":null,"abstract":"<p><p>Deep eutectic solvents (DESs) have garnered significant attention in pharmaceutical research in recent years due to their high efficiency, facile separability and biocompatibility. Characterised by hydrogen-bond donors (HBDs) and hydrogen-bond acceptors (HBAs), DESs exhibit low toxicity, favourable biodegradability, and excellent solubilising properties, rendering them promising alternatives to conventional organic solvents in drug synthesis, natural active ingredient extraction and drug delivery. This review systematically evaluates the broad pharmaceutical applications of DESs, with particular emphasis on enhanced drug solubility and bioavailability. In plant extraction, DESs outperform traditional solvents (<i>e.g</i>., diethyl ether) by improving the recovery efficiency of bioactive compounds. In drug synthesis, certain DESs function simultaneously as reaction media and catalysts, enhancing reaction efficiency and selectivity while minimising environmental impact. In drug delivery, DESs facilitate transdermal and oral absorption through interactions with biological membranes, making improved delivery efficiency. Despite these advantages, challenges remain, including high viscosity, formulation complexity, and unresolved regulatory considerations. Future research must focus on physico-chemical optimisation, safety evaluation, and scalable production to fully realise the potential in pharmaceutical applications.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":" ","pages":"1-22"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148040227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting atherosclerotic inflammation: Advances in NLRP3 inflammasome inhibitors beyond LDL-C.","authors":"Ligang Bao, Xialing Dai","doi":"10.2478/acph-2026-0019","DOIUrl":"https://doi.org/10.2478/acph-2026-0019","url":null,"abstract":"<p><p>Atherosclerosis, the main pathological background of cardiovascular diseases, is not only characterized by lipid metabolism disorders but also chronic inflammation as a major driver of disease progression. As a key regulator of inflammatory immune responses, the NLRP3 inflamma-some is involved in the development and instability of atherosclerotic plaques. Although reducing low-density lipoprotein cholesterol (LDL-C) confers benefits, residual cardiovascular risk persists, necessitating novel anti-inflammatory therapies. This review provides a comprehensive overview of NLRP3 inflammasome activation mechanisms and its role in plaque inflammation. We systematically summarize current NLRP3 inhibitors under preclinical and clinical development, including small molecules and biologics, with emphasis on design strategies, structural characteristics and pharmacological activities. Challenges in clinical translation, such as tissue targeting and safety, are also discussed. By integrating recent advances in molecular mechanisms and medicinal chemistry, this article aims to provide a theoretical basis for targeted anti-inflammatory therapies beyond lipid lowering.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-16"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SEM/EDS analysis as a complementary tool for continuous improvement of cefixime granules for oral suspension.","authors":"Ivana Mitrevska, Dino Karpicarov, Ana Mihailovska, Dejan Mirakovski, Olivera Paneva, Gjorgji Petrushevski","doi":"10.2478/acph-2026-0018","DOIUrl":"https://doi.org/10.2478/acph-2026-0018","url":null,"abstract":"<p><p>The aim of this study was to evaluate scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectroscopy (EDS) as complementary analytical tools for supporting continuous improvement in pharmaceutical granule manufacturing. Pilot-scale cefixime granules for oral suspension were prepared as defined process scenarios, including placebo, reference, intermediate, stress-exposed, and optimised batches. SEM was used to compare granule morphology, surface integrity, and agglomeration behaviour, whereas EDS provided qualitative and semi-quantitative information on localised elemental composition, with emphasis on sulfur as an API-related marker and oxygen-to--sulfur trends as surface-sensitive indicators of process- or stress-related variability. Intermediate and stress-exposed batches showed increased surface roughness, microstructural deterioration, and higher oxygen-to-sulfur ratios, whereas reference and optimised batches showed more uniform morphology and comparable elemental profiles. The findings indicate that SEM/EDS can provide useful material-level insight into process-related variability and may support root--cause investigation and process refinement. Overall, SEM/EDS is proposed as a complementary, localised, and semi-quantitative approach for supporting continuous improvement in pharmaceutical granule manufacturing.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-11"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recurrent urinary tract infections in older adults: A systematic review of current challenges and emerging therapeutic strategies.","authors":"Junmei Lv, Ajaz Ahmad Waza","doi":"10.2478/acph-2026-0017","DOIUrl":"10.2478/acph-2026-0017","url":null,"abstract":"<p><p>As global life expectancy continues to rise, urinary tract infections (UTIs) have become an increasing concern in older adults. The higher prevalence in this population is attributed to anatomical and physiological changes of the urinary tract, hormonal imbalances, immunosenescence, and the presence of comorbidities. These factors, combined with a distinct microbiological profile and rising antimicrobial resistance, create significant clinical challenges in diagnosis and treatment. We conducted a systematic review of clinical trials and observational studies on the epidemiology, pathogenesis, diagnosis, and management of recurrent urinary tract infections (rUTIs) in older adults. The prevalence of rUTIs increases with age, disproportionately affecting women, with 53 % of those over 55 years experiencing recurrences within one year. Healthcare-associated UTIs (HAUTIs) account for 20-30 % of nosocomial infections, primarily impacting older adults. The host microbiome seemed crucial in UTI pathogenesis, with <i>Escherichia coli</i> being the leading causative agent due to its ability to adhere, colonise, and evade the immune response. In elderly patients, atypical presentations - such as delirium, functional decline, or nonspecific abdominal symptoms - complicate diagnosis, underscoring the critical need to differentiate symptomatic infections from asymptomatic bacteriuria (ASB) to prevent misdiagnosis and overtreatment. Effective management requires accurate diagnosis, appropriate antibiotic selection, and careful monitoring of adverse effects, especially in patients with comorbidities. Emerging therapies, including faecal microbiota transplantation, bacteriophages, probiotics, and proanthocyanidins, offer promising adjuncts. While long-term antibiotic prophylaxis is effective, it increases the risk of bacterial resistance, particularly in catheterised patients. Behavioural modifications, such as increased fluid intake, aid pathogen clearance, and topical estrogen therapy in postmenopausal women provides additional preventive benefit. Managing recurrent UTIs in ageing populations requires addressing microbiological, diagnostic, and antimicrobial resistance challenges. Despite resistance levels, the first-line treatment, nitrofurantoin, remains a viable therapeutic option, particularly in developed countries. An integrated approach combining individualised care, healthcare provider training, and rational antimicrobial use is essential to improving patient outcomes and quality of life. Future strategies should focus on novel antimicrobials targeting bacterial virulence factors, vaccines against uropathogens, and advanced diagnostic technologies.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-25"},"PeriodicalIF":1.8,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of piperine combined with luteolin on anti-non-small cell lung cancer activity\u0000 <i>in vitro</i>\u0000 and in LLC tumour-bearing mice: Mechanistic insights from network pharmacology and molecular docking","authors":"Liangfeng Wang, Yuexing Chang, Yufeng Liu, Ailing Guo, Baorong Wang, Feng Jin, Yun Deng","doi":"10.2478/acph-2026-0015","DOIUrl":"https://doi.org/10.2478/acph-2026-0015","url":null,"abstract":"","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 2","pages":"1-26"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148394332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of astragaloside IV on a model of isoproterenol-induced hypertrophic injury in H9c2 cells.","authors":"Yang Long, Yuan Xiao, Chun Chen, Chao Peng, Yuxi Zhang","doi":"10.2478/acph-2026-0006","DOIUrl":"10.2478/acph-2026-0006","url":null,"abstract":"<p><p>The objective of this study was to explore the protective effect of astragaloside IV on a model of isoproterenol-induced (ISO) hyper-trophic injury in rat cardiomyocytes H9c2 (cell line derived from embryonic BD1X rat heart tissue). A cell hypertrophy injury model was established (H9c2 cells treated with 100 μmol L-1 ISO). The cells were divided into normal control, a model group, and an astragalo-side IV group at several concentrations. Astragaloside IV was pre-administered for 2 hours, followed by ISO treatment for 24 hours. Cell viability, cell surface area, apoptosis rate, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS), superoxide dismutase (SOD), the mRNA levels of Bcl-2, Bax, p62, and LC3, the protein expressions of Sirt1, p62, caspase-3, beclin, and p53 and the LC3II/LC3I ratio were detected. Astragaloside IV significantly alleviated ISO-induced hypertrophy injury in H9c2 cells, reduced cell surface area and LDH release, decreased apoptosis rate and intracellular ROS levels, increased SOD levels, upregulated the expressions of autophagy-related mRNA and proteins, and downregulated the expressions of apoptosis-related mRNA and proteins. Astragaloside IV can effectively inhibit ISO-induced hypertrophy and apoptosis in H9c2 cells, and its mechanism may be related to promoting auto-phagy and reducing oxidative stress.</p>","PeriodicalId":7034,"journal":{"name":"Acta Pharmaceutica","volume":"76 1","pages":"1-12"},"PeriodicalIF":1.8,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147508729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}