{"title":"Advanced approaches for selective investigation of neuronal function and circuitry: The future of developing novel therapeutic strategies in neuropharmacology?","authors":"S. Joksimović, S. Joksimovic","doi":"10.5937/arhfarm73-43104","DOIUrl":"https://doi.org/10.5937/arhfarm73-43104","url":null,"abstract":"Recent advances in neuroscience techniques and methods ushered in a new era in the research of neuronal function with unprecedented selectivity and temporal resolution. One of the main characteristics of these technical advances is the ability to selectively target and/or modulate specific neuronal subpopulations and circuits in both healthy and diseased brains. Although initially designed as tools to help researchers better understand the mechanisms underlying neuronal activity and complex behaviors, these novel approaches may also accelerate the process of drug discovery in many areas of neuroscience, and some may even potentially serve as novel therapeutic strategies. The application of different electrophysiological techniques is still considered essential in studying ion channel function and pharmacology, as well as network-level changes in brain activity. The cutting-edge methods for investigation of brain function include opto-and chemogenetics in freely behaving animals; both approaches enable highly selective control of neuronal activity using either a light stimulation (optogenetics) or a chemical ligand (chemogenetics) in both loss-and gain-of-function experiments. In this review paper, we aim to summarize recent scientific evidence on the state-of-the-art and provide information on these advances, taking into account both academic and pharmaceutical industry points of view.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KEAP1/NRF2 as a druggable target","authors":"A. Dinkova-Kostova","doi":"10.5937/arhfarm73-43475","DOIUrl":"https://doi.org/10.5937/arhfarm73-43475","url":null,"abstract":"Nuclear factor erythroid 2-related factor 2 (NRF2; encoded by NFE2L2) is an inducible transcription factor that regulates the expression of a large network of genes encoding proteins with cytoprotective functions. NRF2 also has a role in the maintenance of mitochondrial and protein homeostasis, and its activation allows adaptation to numerous types of cellular stress. NRF2 is principally regulated at the protein stability level by three main ubiquitin ligase systems, of which the regulation by Kelch-like ECH-associated protein 1 (KEAP1), a substrate adaptor protein for Cul3/Rbx1-based ubiquitin ligase, is best understood. KEAP1 is a multi-functional protein and, in addition to being a substrate adaptor, it is a sensor for electrophiles and oxidants. Pharmacological inactivation of KEAP1 has protective effects in animal models of human disease, and KEAP1 is now widely recognized as a drug target, particularly for chronic diseases, where oxidative stress and inflammation underlie pathogenesis. Many compounds that target KEAP1 have been developed, including electrophiles that bind covalently to cysteine sensors in KEAP1, non-electrophilic protein-protein interaction inhibitors that bind to the Kelch domain of KEAP1, disrupting its interaction with NRF2, and most recently, heterobifunctional proteolysistargeting chimeras (PROTACs) that promote the proteasomal degradation of KEAP1. The drug development of KEAP1-targeting compounds has led to the entry of two compounds, dimethyl fumarate (BG-12, Tecfidera®) and RTA-408 (omaveloxolone, SKYCLARYS®), in clinical practice. In 2013, dimethyl fumarate was licenced as the first oral first-line therapy for relapsingremitting multiple sclerosis and is also used for the treatment of moderate-to-severe plaque psoriasis. In February 2023, omaveloxolone was approved by the United States Food and Drug Administration as the first and only drug for patients with Friedreich's ataxia.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Zavišić, S. Ristić, Branka Petković, Dragoslava Živkov-Šaponja, Nikola Jojić, D. Janković
{"title":"Microbiological quality of probiotic products","authors":"G. Zavišić, S. Ristić, Branka Petković, Dragoslava Živkov-Šaponja, Nikola Jojić, D. Janković","doi":"10.5937/arhfarm73-42160","DOIUrl":"https://doi.org/10.5937/arhfarm73-42160","url":null,"abstract":"Microorganisms used as probiotics should meet elementary safety aspects (non-toxicity, absence of antibiotic resistance genes and translocation) and functional/technological aspects (resistance and survival in the acid gastric environment, adhesiveness, stability, and cell viability). Probiotics with the health claim of being a dietary product or a pharmabiotic (drug category) should be clinically tested, validated, documented, and continuously controlled for quality. Important quality parameters include the identification of declared probiotic strains, the number of viable microorganisms (probiotic bacteria and/or fungi), and microbiological purity (absence of specified pathogenic/opportunistic pathogenic bacteria and fungi, and limitation of total unspecified contaminants such as aerobic bacteria, yeasts, and molds). Due to numerous reports of low-quality commercial probiotics marketed for human use, this review discusses the methods used to test the probiotic microorganism content, safety for the intended use, and proven health benefits of those probiotics whose microbiological quality deviates from the manufacturer's stated content, as well as the maintenance of cell viability, i.e., stability of the probiotic during the shelf life. In addition, the adverse effects of probiotics and the potential hazards to the health of the user are addressed.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development and validation of a stability-indicating RP-HPLC method for determination of aripiprazole and its degradation products","authors":"V. Mijatović, M. Zečević, J. Zirojević","doi":"10.5937/arhfarm73-44512","DOIUrl":"https://doi.org/10.5937/arhfarm73-44512","url":null,"abstract":"The goal of this study was the optimization of chromatographic conditions and validation of the isocratic RP-HPLC method for monitoring the stability of aripiprazole, identification and quantitative analysis of aripiprazole and its degradation products in tablets. In addition, robustness was tested by applying the methodology of experimental design. The forced degradation study of aripiprazole was conducted in accordance with the ICH guidelines. The stability of the active pharmaceutical substance was tested under the conditions of hydrolysis in acidic, neutral and basic environments, thermal degradation, oxidation and photolysis. The active pharmaceutical ingredient was degraded under oxidation conditions, and the identity of the resulting degradation product, N-oxide, was confirmed. Under the other conditions tested, the active pharmaceutical substance was found to be stable. The developed method RP-HPLC allowed the separation of degradation products and aripiprazole and was defined as a stability-indicating method. The proposed method was validated for qualitative and quantitative analysis of aripiprazole and its degradation products. Accordingly, selectivity, linearity, precision, accuracy, limit of detection, limit of quantification, and robustness of the method were tested. The Box-Behnken experimental design was used in robustness testing.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tijana Stanković, Tanja Ilić, Vladimir Dobričić, Anđela Tošić, Ivana Pantelić, Snežana Savić
{"title":"Biocompatible lipid nanocarriers for improved skin delivery of fluocinolone acetonide: Physicochemical and in vitro performances","authors":"Tijana Stanković, Tanja Ilić, Vladimir Dobričić, Anđela Tošić, Ivana Pantelić, Snežana Savić","doi":"10.5937/arhfarm73-46312","DOIUrl":"https://doi.org/10.5937/arhfarm73-46312","url":null,"abstract":"In order to improve the delivery of topical corticosteroids into inflammatory skin lesions while reducing the likelihood of adverse effects, lipid nanocarriers have received increasing attention. Hence, this study aimed to develop biocompatible nanoemulsions (NEs) and nanostructured lipid carriers (NLCs) as carriers for fluocinolone acetonide (FA) by carefully optimizing the formulation and process parameters. After an analysis of the relevant physicochemical parameters and stability testing, in vitro release and permeation tests were performed to evaluate whether the nanocarriers affected the penetration of FA into/through the skin compared to a conventional reference product (Sinoderm® cream). The developed NEs exhibited satisfactory physicochemical properties (droplet size <200 nm, PDI<0.2, ZP>|-30| mV, pH ~ 4.75) and long-term stability. Although the developed NLCs initially had satisfactory properties, gelation was observed within 3 months of storage, implying that further formulation testing is required to resolve the limited stability of these systems. In vitro release/permeation findings suggest that the developed nanocarriers (especially NEs) provide better delivery of FA into/though the skin compared to the Sinoderm® cream. Therefore, a lecithin-based NE with a 10% lipid phase (medium-chain triglycerides/oleic acid 3:1) is a promising strategy for improved delivery of FA to the inflamed skin, allowing for ease of application, especially to larger skin surfaces and hairy regions.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"155 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134981819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dietary antioxidants and health effects: What are their optimal intakes?","authors":"B. Vidović","doi":"10.5937/arhfarm73-45552","DOIUrl":"https://doi.org/10.5937/arhfarm73-45552","url":null,"abstract":"A well-balanced diet provides many compounds with antioxidant properties, such as vitamins, minerals, provitamins (e.g., b-carotene), and phytochemicals (e.g., carotenoids, polyphenols, organosulfur compounds). In addition to direct antioxidants, foods indirectly support the endogenous defense system, by providing substrates for the synthesis of glutathione, antioxidant defense enzymes, metal-binding proteins, or modulators of redox-dependent signaling pathways. Epidemiological studies indicate that higher intakes and circulating concentrations of vitamins C, E, carotenoids, and flavonoids reflect a lower risk of chronic diseases and all-cause mortality, suggesting the importance of optimal intakes of these substances. However, unlike antioxidant micronutrients, phytochemicals have no defined recommended intake levels. A diet should be based on consuming various plant foods (fruit, vegetables, legumes, whole grains, seeds, nuts), antioxidant-rich beverages, and a moderate intake of animal food products to fully exploit the health-promoting effects of dietary antioxidants.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Kostadinović, V. Popadić, S. Klašnja, A. Klisic, J. Kotur-Stevuljević, Z. Andrić, M. Zdravković
{"title":"Cardiotoxicity: Importance of biomarkers","authors":"J. Kostadinović, V. Popadić, S. Klašnja, A. Klisic, J. Kotur-Stevuljević, Z. Andrić, M. Zdravković","doi":"10.5937/arhfarm73-40534","DOIUrl":"https://doi.org/10.5937/arhfarm73-40534","url":null,"abstract":"The clinical efficacy of chemotherapy, as a recognized therapeutic approach for malignant diseases, usually has certain limitations due to its cardiotoxicity (CT) and consequent cardiomyopathy, or even heart failure. CT is defined as any cardiac injury connected with oncology treatment, whether it is chemo-, radio-, targeted or immunotherapy, or cancer by itself, and it represents a great challenge for clinicians in everyday practice. A wide spectrum of factors related to chemotherapy (type of drug, dose during each cycle, cumulative dose, schedule, method of application, combination with other cardiotoxic drugs or association with radiotherapy) and patient characteristics (age, presence of cardiovascular risk factors, previous cardiovascular disease) are the determining factors that influence the frequency of CT. Imaging methods for morphological and functional monitoring of the heart muscle are used for monitoring CT. The quest for diagnostic tools for early CT detection is of great significance. In line with this, the measurement of some cardiac biomarkers has found its place in clinical settings as an early determinant of myocardial injury. Therefore, in this review article, special attention will be paid to certain well-established, as well as certain novel cardiac biomarkers, and their role in recognizing asymptomatic CT, in order to gain deeper insight into their diagnostic utility.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The landscape of nanomedicines: An expert perspective","authors":"Ines Nikolić, Brankica Filipić, Marija Petrović, Olivier Jordan, Snežana Savić, Gerrit Borchard","doi":"10.5937/arhfarm73-46686","DOIUrl":"https://doi.org/10.5937/arhfarm73-46686","url":null,"abstract":"The field of nanotechnology is at the forefront of a scientific revolution, where the term \"nano\" transcends mere size and opens the door to enormous possibilities. In the context of drug development, the selection of a suitable drug delivery system (corresponding to a certain active pharmaceutical ingredient) is a pivotal decision. Accordingly, nanosystems have emerged as a promising avenue, offering innovative solutions, and gaining recognition for addressing healthcare issues. While these products hold immense promise, they have faced certain complexities in their translation from the preclinical to the clinical setting, reflected in the lack of proper assessment protocols for quality and safety aspects and, consequently, an insufficiently defined regulatory environment. Since the groundbreaking US Food and Drug Administration (FDA) approval of liposomal doxorubicin in 1995, approximately 80 nanomedicine products have received regulatory approval so far. Recent attention has gravitated toward lipid-based nanomedicines, particularly in the development of mRNA vaccines during the COVID-19 pandemic, further highlighting their significance. However, the relatively modest number of approved nanomedicines compared to the extensive research efforts raises important questions and underscores areas of uncertainty. This article provides an overview of the challenges in defining nanomedicines, their properties, the complexities of regulatory frameworks, and the imperative for standardized characterization protocols.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134982045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrijana Milošević-Georgiev, Dragiša Obradović, Dušanka M. Krajnović
{"title":"Smoking cessation service in the pharmacy setting: Attitudes of pharmacy students, pharmacists and the general public","authors":"Andrijana Milošević-Georgiev, Dragiša Obradović, Dušanka M. Krajnović","doi":"10.5937/arhfarm73-44687","DOIUrl":"https://doi.org/10.5937/arhfarm73-44687","url":null,"abstract":"Smoking is a global public health problem, and control measures should be implemented in the community so as to reduce the number of smoking-related diseases and healthcare costs. Community pharmacies are ideal places for providing tobacco cessation counselling as a type of public health service, because they are the most accessible health facilities with direct contact with patients. We aimed to examine attitudes towards the implementation of such services, conducting surveys on a sample of pharmacy students (N=300), community pharmacists (N=383) and the general public (N=987) in the Republic of Serbia. The introduction of smoking cessation services at pharmacies was supported by pharmacy students (59.7%), pharmacists (49.2%), and the general public (36.7%). No difference was found between pharmacistsàttitudes in terms of their gender, age, level of education and years of experience. We found evidence that pharmacists as public health practitioners were recognized mostly by students (94.3%). The majority of them (86.3%) recognized the need for additional education in order to implement new services, and every third pharmacist recognized a gap in their education. The data indicate the need for directed research in order to explore the educational needs and competences for practicing pharmacists and enable them to perform services such as smoking cessation in the future.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hydrogen sulfide-releasing therapeutics: How far have we come in clinical studies?","authors":"M. Marinko, A. Novaković","doi":"10.5937/arhfarm73-44691","DOIUrl":"https://doi.org/10.5937/arhfarm73-44691","url":null,"abstract":"Hydrogen sulfide (H 2 S) is the youngest member of the gasotransmitters family consisting of nitric oxide (NO) and carbon monoxide (CO). This signalling molecule is implicated in the regulation of a wide range of processes, such as inflammation, pain, and tissue repair, and has an important role in signalling processes affecting cardiovascular health, either as an independent effector or as an enhancer of the NO system. With the discovery of the H 2 S role in the pathogenesis of many diseases, the development of new pharmaceuticals that could be useful in conditions with disturbed levels of endogenous H 2 S began. Today, the development of H 2 S-releasing drugs has reached the level of clinical studies. Drugs such as SG1002, aimed at the treatment of heart failure, and ATB-346, aimed at the treatment of arthritis, have been tested in Phase I/II clinical studies and have shown significant therapeutic potential. Additionally, it has been shown that some already known drugs, such as zofenopril, produce part of their beneficial effects by releasing H 2 S. Evidence from clinical studies presented in this paper encourages further clinical testing of H 2 S-based therapeutics and the possibility of their application in a wide range of diseases, such as hypertension, diabetes and chronic kidney disease.","PeriodicalId":39173,"journal":{"name":"Arhiv za Farmaciju","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71199791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}