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Nature based tourism in the slunjsko-plitvička area
No full textOvaj rad istražuje turizam temeljen na prirodi u slunjsko-plitvičkom kraju, s naglaskom na povezanost Nacionalnog parka Plitvička jezera s ostalim atrakcijama u blizini. Cilj istraživanja bio je analizirati motivaciju, aktivnosti, obilježja putovanja i zadovoljstvo posjetitelja, kao i ispitati turističku ponudu i infrastrukturu ovog područja. Podaci su prikupljeni putem anketnog istraživanja posjetitelja Nacionalnog parka i Rastoka. Rezultati istraživanja pokazuju visoko zadovoljstvo posjetitelja s prirodnim ljepotama i kulturnom baštinom, no također ukazuju na nedostatak koordinacije između različitih turističkih lokaliteta, što može rezultirati fragmentiranim iskustvom za posjetitelje. Iako postoje jasne prednosti u prirodnim resursima, infrastruktura nije dovoljno razvijena i usklađena s potrebama svih dionika, a povećan turistički pritisak stvara izazove u održavanju i očuvanju tih resursa. Istraživanje naglašava potrebu za integracijom svih ključnih atrakcija u jedinstvenu ponudu, koja bi omogućila lakšu povezanost između lokaliteta, te za održivim razvojem turizma koji poštuje prirodne i kulturne vrijednosti. Daljnji razvoj trebao bi uključivati bolju suradnju između lokalne zajednice, pružatelja usluga i turističkih dionika, čime bi se stvorila dugoročna održivost ovog područja.This thesis explores nature-based tourism in slunjsko-plitvička area, with a focus on the connection between Plitvice Lakes National Park and other nearby attractions. The aim of the research was to analyse visitor motivation, activities, travel characteristics, and satisfaction, as well as to examine the tourism offerings and infrastructure of the region. Data was collected through a survey conducted with visitors of Plitvice Lakes National Park and Rastoke. The findings show high visitor satisfaction with the natural beauty and cultural heritage, but also point to a lack of coordination between various tourist sites, which can result in a fragmented experience for visitors. While there are clear advantages in natural resources, the infrastructure is not sufficiently developed and aligned with the needs of all participants, and increased tourist pressure creates challenges in maintaining and preserving these resources. The research highlights the need to integrate all key attractions into a unified offering, which would improve connectivity between sites, and for sustainable tourism development that respects natural and cultural values. Further development should include better collaboration between the local community, service providers, and tourists, creating long-term sustainability for the area
Leishmaniosis - Types And Diagnostics
No full textLišmanioza je invazijska bolest ljudi i mnogih vrsta životinja koja je uzrokovana parazitima
iz roda Leishmania. Opisano je tridesetak vrsta i podvrsta iz roda, a njih dvadesetak uzrokuje bolest
kod ljudi (zoonoze). Lišmanije se razvijaju preko biološkog vektora, a nalazimo ih u dva oblika
(promastigotni i amastigotni oblik). Vektori lišmanioze su hematofagni insekti tzv. papatači iz
rodova Phlebotomus i Lutzomyia. Kod ljudi, lišmanioza se pojavljuje u nekoliko oblika: kožna,
kožno – sluznička te visceralna, a psi su najvažniji rezervoari bolesti te najveća opasnost za ljude.
Lišmanije se mogu prenositi i transfuzijom krvi i krvnih derivata, transplacentarno te spolnim
putem. Kod invadiranih pasa klinička slika varira od blage, pa sve do jake kliničke manifestacije i
uginuća. Uključeni su kožno-sluzničko-visceralni simptomi. Lišmaniozu je moguće
dijagnosticirati direktnim putem, tj. parazitološkim nalazom uzročnika u obojenom uzorku
punktata limfnih čvorova, koštane srži, slezene ili jetre te in vitro kultivacijom u hranjivim
podlogama. Indirektno je moguće dokazati bolest dokazujući protutijela s različitim serološkim
metodama kao što su indirektna imunofluorescencija, imunoenzimski test, imunokromatografski
test, direktna aglutinacija te western-blotting. Bilo koja metoda dijagnostike je adekvatna ako se
koristi u kombinaciji s kliničkom slikom.Leishmaniosis is an invasive disease of humans and many animal species, which is caused
by parasites from the genus Leishmania. About thirty species and subspecies of the genus have
been described, and about twenty of them cause the disease in humans (zoonoses). Leishmaniosis
develops through an biological vector, and can be found in two forms (promastigote and amastigote
form). The vectors of leishmaniosis are hematophagous insects, sandflies from Phlebotomus and
Lutzomyia genera. In humans, leishmaniosis appears in several forms: cutaneous, muco-cutaneous
and visceral form. Dogs are the most important reservoir of the disease and are the greatest danger
to humans. Leishmania can be transmitted by transfusion of blood and blood derivatives,
transplacentally and sexually. In infected dogs, clinical signs vary from mild, to severe clinical
manifestations and death. Cutaneous, muco-cutaneous and visceral symptoms are involved.
Leishmaniosis can be diagnosed directly, i. e. by parasitological detection of the causative agent in
stained lymph node, bone marrow, spleen or liver biopsy sample and by in vitro cultivation in in
vitro culture. Indirectly is possible to prove diseases by proving the antibodies with different
serological methods such as indirect immunofluorescence, immunoenzymatic test,
immunochromatographic test, direct agglutination and western-blotting. Any diagnostic method is
adequate if used in combination with the clinical pictur
Development and validation of UHPLC method for purity determination of active pharmaceutical substance of an antirheumatic drug
No full textKvaliteta i sigurnost lijekova ovise o preciznoj kontroli njihovih sastavnica, osobito farmaceutika. Antireumatski lijekovi koji se koriste u terapiji reumatoidnog artritisa zahtijevaju razvoj analitičkih metoda za pouzdano određivanje njihove čistoće i prisutnosti poznatih onečišćenja. U cilju osiguranja kvalitete i sigurnosti primjene lijeka, nužno je razviti selektivnu i osjetljivu analitičku metodu za pouzdano određivanje poznatih onečišćenja prisutnih u farmaceutiku. U ovom radu razvijena je i validirana UHPLC metoda za određivanje čistoće farmaceutika. Validacija je provedena u skladu s ICH smjernicama i obuhvatila je ispitivanje specifičnosti, linearnosti, preciznosti (ponovljivosti), točnosti, granice detekcije, granice kvantifikacije, radnog područja, stabilnosti otopina te robusnosti. Rezultati su pokazali da je metoda pouzdana, osjetljiva i prikladna za rutinsku primjenu u kontroli kvalitete djelatne tvari.The quality and safety of drugs depend on precise control of their components, particularly the pharmaceutical substances. Antirheumatic drugs used in the treatment of rheumatoid arthritis require the development of analytical methods for the reliable determination of their purity and the presence of known impurities. To ensure drug quality and safety, it is essential to develop a selective and sensitive analytical method for the reliable determination of known impurities present in the pharmaceutical substance. In this study, a UHPLC method was developed and validated for the determination of the pharmaceutical's purity. The validation has been conducted in accordance with ICH guidelines and included evaluation of specificity, linearity, precision (repeatability), accuracy, detection limit, quantification limit, working range, solution stability, and robustness. The results demonstrated that the method is reliable, sensitive, and suitable for routine application in quality control of the active pharmaceutical ingredient
Evaluating the effect of Republic of Croatia's accession to the European Union on housing market value
No full textPristupanje Republike Hrvatske Europskoj uniji 2013. godine imalo je izražen ekonomski, pravni i investicijski učinak, s posebnim odrazom na tržište nekretnina. Ovaj rad istražuje utjecaj tog procesa na vrijednost stambenih nekretnina u Hrvatskoj, s naglaskom na promjene cijena prije i nakon ulaska u EU te identifikaciju ključnih čimbenika koji su oblikovali te promjene. Teorijski dio rada obuhvaća definiranje temeljnih ekonomskih pojmova relevantnih za tržište nekretnina, kao i analizu učinaka međunarodnih integracija na nacionalni nekretninski sektor. U analitičkom dijelu razmatraju se makroekonomski pokazatelji, zakonodavne promjene te uloga stranih investitora. Korištenjem statističkih podataka, korelacijske i komparativne analize istražuju se regionalne razlike u kretanju cijena stambenih nekretnina, s posebnim osvrtom na Zagreb, jadransku obalu i kontinentalnu Hrvatsku. Rezultati ukazuju na porast interesa stranih ulagača nakon pristupanja EU, povećanu potražnju i rast cijena, osobito u urbanim i turistički atraktivnim područjima. Istodobno, analiza potvrđuje izražene regionalne disparitete te utjecaj dodatnih faktora poput gospodarskog rasta, kreditne politike i demografskih kretanja. Rad nudi cjelovit prikaz učinaka europskih integracija na hrvatsko tržište nekretnina te predlaže smjernice za daljnja istraživanja i oblikovanje održivih ekonomskih politika u sektoru nekretnina.The accession of the Republic of Croatia to the European Union in 2013 had a significant economic, legal, and investment impact, with a particularly pronounced effect on the real estate market. This paper examines the influence of this process on the value of residential real estate in Croatia, focusing on price trends before and after EU accession, as well as identifying the key factors that have shaped these changes. The theoretical section of the paper defines fundamental economic concepts relevant to the real estate market and analyses the effects of international integration on the national property sector. The analytical part explores macroeconomic indicators, legislative changes, and the role of foreign investors. Using statistical data, correlation and comparative analysis, the research investigates regional differences in residential property price movements, with particular attention to Zagreb, the Adriatic coast, and continental Croatia. The findings indicate a rise in foreign investor interest following EU accession, an increase in demand, and a consequent rise in prices—especially in urban and tourist-attractive areas. At the same time, the analysis confirms notable regional disparities and the influence of additional factors such as economic growth, credit policy, and demographic trends. The paper provides a comprehensive overview of the effects of European integration on the Croatian real estate market and offers recommendations for further research and the formulation of sustainable economic policies within the real estate sector
The economic impact of the natural gas market on the economy of the European union
No full textTema Ekonomski utjecaj tržišta prirodnog plina na Europsku uniju izuzetno je relevantna i aktualna, osobito u kontekstu globalnih promjena u energetskoj politici, geopolitičkim napetostima i klimatskim izazovima. Tržište prirodnog plina igra ključnu ulogu u energetskoj stabilnosti EU-a, budući da je prirodni plin jedan od najvažnijih izvora energije koji pokreću industriju, grijanje, električnu energiju, te mnoge druge sektore. Europska unija se suočava s potrebom smanjenja ovisnosti o fosilnim gorivima, dok istovremeno nastoji osigurati stabilnu opskrbu plinom, što je postalo još značajnije zbog utjecaja rata u Ukrajini na energetsku sigurnost i cijene plina. Cilj ovog završnog rada je analizirati ekonomske aspekte tržišta prirodnog plina u Europskoj uniji, s posebnim naglaskom na njegove utjecaje na gospodarstvo članica EU-a. Kroz analizu, cilj je odgovoriti na pitanje: Kako tržište prirodnog plina utječe na ekonomske uvjete u EU-u, s obzirom na promjenjivu geopolitiku, cijene plina, te energetske politike koje se provode? Rad će se usmjeriti na analizu ključnih čimbenika koji oblikuju tržište plina, uključujući: utjecaj vanjskih faktora (kao što su političke odluke i globalna potražnja) na cijene i dostupnost plina, analizu energetske sigurnosti i strategije EU-a u pogledu opskrbe plinom, utjecaj rasta cijena na industriju, potrošnju i konkurentnost EU-a, korelaciju između dekarbonizacije i tržišta plina, te prijelaza na obnovljive izvore energije. Metodologija istraživanja koju ću koristiti u ovome radu su sekundarne podatke, kvantitativna analiza, kvalitativna analiza i studije slučajaThe economic impact of the natural gas market on the European Union is extremely relevant and current, especially in the context of global changes in energy policy, geopolitical tensions, and climate challenges. The natural gas market plays a key role in the energy stability of the EU, as natural gas is one of the most important energy sources that powers industry, heating, electricity, and many other sectors. The European Union is facing the need to reduce dependence on fossil fuels while simultaneously striving to ensure a stable gas supply, which has become even more significant due to the impact of the war in Ukraine on energy security and gas prices. The aim of this thesis is to analyze the economic aspects of the natural gas market in the European Union, with a particular focus on its impacts on the economies of EU member states. Through the analysis, the goal is to answer the question: How does the natural gas market affect the economic conditions in the EU, considering the changing geopolitics, gas prices, and energy policies being implemented? The paper will focus on analyzing the key factors shaping the gas market, including: the influence of external factors (such as political decisions and global demand) on gas prices and availability, an analysis of energy security and the EU's strategies regarding gas supply, the impact of rising prices on industry, consumption, and EU competitiveness, the correlation between decarbonization and the gas market, and the transition to renewable energy sources. The research methodology I will use in this paper includes secondary data, quantitative analysis, qualitative analysis, and case studies
Influence of process parameters on removal of acetamiprid with NF and RO membranes
No full textPesticidi i antiparazitici su toksični organski spojevi koji su zbog široke i rastuće primjene česta onečišćivala voda te kao takvi predstavljaju globalan ekološki i javnozdravstveni problem. Dodatni problem je činjenica da se ne mogu ukloniti konvencionalnim široko dostupnim procesima pročišćavanja voda. Tlačni membranski procesi su se pokazali učinkovitim, održivim procesima za separaciju ovakvih organskih spojeva iz voda, a postoji i potencijal za široku primjenu daljnjom optimizacijom procesa. U ovom radu se provelo ispitivanje utjecaja procesnih parametara (tlaka: 5, 10 i 15 bar i brzine strujanja: 2, 3 i 4 L/min) na učinkovitost separacije acetamiprida iz vodene otopine nanofiltracijom (NF) i reverznom osmozom (RO) u svrhu određivanja optimalnih uvjeta. Primjenom optimalnih uvjeta ispitana je učinkovitost separacije odabranih pesticida (tiakloprid i klotianidin) kao i antiparazitika (albendazol, febantel i mebendazol). Također je pri optimalnim uvjetima određena učinkovitost separacije smjese pesticida i antiparazitika. Učinkovitost separacije je analizirana tekućinskom kromatografijom visoke učinkovitosti. Separacija acetamiprida s NF provedena pri niskom radnom tlaku 5 bar pokazuje najlošije rezultate uspješnosti separacije u iznosu od 55 % do 65 %, dok pri višim tlakovima i brzinama strujanja pokazuje uspješnost separacije veću od 70 %. Separacija acetamiprida RO pokazuje uspješnost separacije veću od 90 % pri svim ispitivanim procesnim parametrima. Određeni su optimalni uvjeti za 1 mg/L otopinu acetamiprida računalnim programom Design Expert 7 i oni iznose: tlak 10 bar i brzina strujanja 4 L/min za NF, tlak 12,5 bar i brzina strujanja 4 L/min za RO proces. Febantel se u potpunosti separira i NF i RO membranom. NF procesom za ostale komponente osim febantela je utvrđena manja uspješnost separacije pri optimalnim uvjetima nego kod acetamiprida. Sve ostale komponente pokazuju uspješnost separacije 95 %) osim za albendazol kod kojeg je iznosila 85,2 %. Obje membrane pokazuju višu učinkovitost separacije komponenti u smjesi nego u binarnim otopinama.Pesticides and antiparasitics are toxic organic compounds which, due to their widespread and increasing use, often pollute water bodies and thus represent a global ecological and health problem. Another problem is the fact that they cannot be removed using conventional, widely used water treatment processes. Pressure-driven membrane processes have proven to be effective and sustainable methods for separating such organic compounds from water, and there is potential for their wider application through further process optimization. In this study, the influence of process parameters (pressure: 5, 10, and 15 bar; flow rate: 2, 3, and 4 L/min) on the removal efficiency of acetamiprid from aqueous solution by nanofiltration (NF) and reverse osmosis (RO) was determined together with optimal conditions. Using optimal conditions, the removal efficiency of selected pesticides (thiacloprid and clothianidin) and antiparasitics (albendazole, febantel, and mebendazole) was investigated. In addition, the efficiency of separation of mixtures of pesticides and antiparasitics was determined under optimal conditions. The removal efficiency was analysed by high-performance liquid chromatography. The separation of acetamiprid by NF at a low operating pressure of 5 bar showed the lowest separation efficiency, ranging from 55% to 65%, while the efficiency at higher pressures and flow rates was above 70%. The removal of acetamiprid by RO showed an efficiency of over 90% for all tested process parameters. The optimal conditions for a 1 mg/L acetamiprid solution were determined using Design Expert 7 software: 10 bar pressure and 4 L/min flow rate for the NF, and 12.5 bar pressure and 4 L/min flow rate for the RO process. Febantel was completely separated from both the NF and RO membranes. For other components (except febantel), the NF process showed lower removal efficiency compared to acetamiprid under optimal conditions. All other components showed removal efficiencies below 55%, indicating that component characteristics need to be considered when optimizing organic pollutant removal. The RO membranes also showed an exceptionally high removal efficiency of over 95% for the other components tested, with the exception of albendazole, for which it was 85.2%. Both membranes showed a higher removal efficiency for components in mixtures than in binary solutions
Photocatalytic degradation of torasemid with photocatalyst with torasemide imprinted molecule
No full textFarmaceutici su biološki aktivne molekule koje se koriste za liječenje, dijagnosticiranje ili sprječavanje bolesti u ljudi te kao promotori rasta u veterini. Njihova kontinuirana uporaba i nepropisano odlaganje dovelo je do povećane količine ovih spojeva u otpadnim komunalnim vodama, iz kojih dospijevaju u okoliš, u kojemu reagiraju s drugim tvarima ostavljajući negativne posljedice na organizme i prirodu. Napredne se oksidacijske metode obrade otpadnih voda kontinuirano ispituju, a kombinacija fotokatalitičke razgradnje uz polimer s otiskom molekule kao fotokatalizator novi je pristup ovoj vrsti obrade. Ovaj rad detaljno prikazuje ispitivanje fotokatalitičke razgradnje torasemida uporabom fotokatalizatora s otiskom molekule torasemida (MIP) pri čemu su usporedno sva ispitivanja provedena i na fotokatalizatoru bez otiska molekule torasemida (NIP). Preliminirani eksperimenti uključivali su adsorpciju za utvrđivanje sorpcijskog ponašanja torasemida na MIP i NIP te fotokatalizu, kako bi se utvrdilo kolika se količina torasemida razgradila više u odnosu na proces bez djelovanja UV zračenja. Utjecaj početnog pH otopine i početne koncentracije torasemida u otopini ispitan je u tri kombinacije pH-vrijednosti (4, 7, 10) pri tri početne koncentracije (5, 10, 15 mg L^-1). Najbrža se razgradnja torasemida odvijala pri početnoj koncentraciji torasemida od 5 mg L^-1 i pH-vrijednosti 4. Konstanta brzine razgradnje za MIP iznosila je 0,0105 min^-1, dok je za NIP iznosila 0,0319 min^-1. Mehanizam fotokatalitičke razgradnje ispitan je scavenging testom, a ispitivani hvatači bili su izopropanol, natrijev azid, mravlja kiselina i para-benzokinon. Eksperimenti su pokazali kako hidroksilni radikali imaju dominantnu ulogu u razgradnji torasemida, bilo da se radi o MIP-u ili NIP-u. Utjecaj matice ispitan je u eksperimentima s dodatkom soli uobičajeno prisutnih u vodi (bikarbonati, nitrati, kloridi i huminska tvar) u ultračistu vodu. Svi su ioni pokazali negativan utjecaj na konstantu brzine razgradnje torasemida, kao i smjesa tih iona. Eksperiment ispitivanja utjecaja smjese farmaceutika (amoksicilin, atenolol, sulfametazin, sulfametoksazol, deksametazon, diklofenak) na brzinu razgradnje rezultirao je najvećim utjecajem, tj. najvećim usporenjem razgradnje torasemida. Procjena toksičnosti smjese torasemida i njegovih razgradnih produkata rezultirala je inhibicijom luminiscencije ispitivane biote (Vibrio fischeri). Svi uzorci analizirani su na HPLC-DAD instrumentu.Pharmaceuticals are bioactive molecules used to treat, prevent or diagnose illnesses in human medicine and as growth-promoting agents in veterinary medicine. Their continuous use and unmonitored disposal have led to their increased appearance in wastewaters. In the environment, they tend to react with other substances, negatively affecting organisms and nature. Advanced oxidation processes for wastewater treatment are continuously being investigated, and the combination of photocatalytic degradation with a molecularly imprinted polymer as the photocatalyst represents a novel approach to this type of treatment. This study provides a detailed analysis of the photocatalytic degradation of torasemide using a molecularly imprinted polymer (MIP) as the photocatalyst. All experiments were conducted using a non-imprinted polymer (NIP) in parallel and compared with the given results. Adsorption and photocatalysis as preliminary experiments determined the sorption affinity of torasemide and its degradation ability compared to the process without UV radiation, using MIP and NIP. The effect of the initial pH and concentration of the analyte was tested via combinations of three initial concentrations (5, 10, 15 mg L^-1) and three pH values (4, 7, 10). The fastest rate of torasemide photocatalytic degradation was observed at a pH value of 4 and the initial concentration of 5 mg L^-1. The degradation rate constant at optimum conditions was 0,0105 min^-1 using MIP and 0,0319 min^-1 using NIP. The mechanism of the photocatalytic degradation was determined through the scavening test using isopropanol, sodium azide, formic acid and para-benzoquinone as scavengers. The experiments showed that hydroxyl radicals play a dominant role in the degradation of torasemide, regardless of whether MIP or NIP was used. The matrix effect was studied using four different salts (bicarbonates, nitrates, chlorides and humic acids), usually present in wastewater. All salts, including their mixture, slowed down the degradation process. The effect of pharmaceutical mixture (amoxicillin, atenolol, sulfamethazine, sulfamethoxazole, dexamethasone, diclofenac) was also investigated and resulted in the slowest rate of all experiments. The toxicity assessment of the mixture of torasemide and its degradation products showed a an inhibition effect on luminescence of the tested biota (Vibrio fischeri). All samples were analyzed using an HPLC-DAD instrument
Preparation and characterization of polysaccharide films via layer-by-layer method
No full textTanki filmovi istražuju se kao sustavi za dostavu lijekova, poput kemoterapeutika. Njihova primjena u obliku premaza za implantate ili samostalnih sustava za dostavu lijekova omogućuje kontrolirano i ciljano otpuštanje kemoterapeutika izravno na mjestu tumora, čime se potencijalno smanjuje toksičnost i poboljšava terapijska učinkovitost. Fitinska kiselina, prirodni antioksidans, prepoznata je po svojoj ulozi u prevenciji i liječenju različitih patoloških stanja i karcinoma. Međutim, potrebno je pripremiti pogodne sustave za njezinu dostavu. Zbog velikog broja hidroksilnih skupina fitiska kiselina posjeduje mogućnost stvaranja stabilnih kompleksa s prirodnim polimerima koji mogu poslužiti kao sustavi za dostavu fitinske kiseline. Biorazgradljivost, biokompatibilnost, antimikrobna svojstva i stabilnost polielektrolitnih kompleksa kitozana i alginata (CA) čine ih pogodnima za biomedicinske primjene. Fizikalnim umreživanjem CA polielektrolitnih kompleksa fitinskom kiselinom moguće je postići antitumorska svojstva tih materijala. Stoga je cilj ovoga rada razviti stabilne tanke filmove na osnovi polielektrolitnih kompleksa kitozan-alginat umreženih fitinskom kiselinom primjenom metode sloj-po-sloj. U ovom radu, ispitan je utjecaj koncentracije otopine fitinske kiseline (0,1, 0,5 i 1,0 mas.%) i vremena umreživanja (3,5 i 7 min) na režim rasta i svojstva dobivenih tankih filmova. Tanki filmovi karakterizirani su ATR-FTIR spektroskopijom kako bi se potvrdilo umreživanje fitinskom kiselinom i ispitala učinkovitost procesa ispiranja tankih filmova nakon pripreme. Morfologija površine i presjeka nakon loma ispitane su SEM analizom. Kapaciteti apsorpcije tankih filmova ispitani su u otopinama fosfatnog pufera (pH 6 i 8) te u fosfatom puferiranoj otopini soli (pH 7,4) tijekom 24 sata. ATR-FTIR spektroskopija potvrdila je umreživanje polielektrolitnog kompleksa CA fitinskom kiselinom, a izostanak apsorpcijskih vrpci otapala ukazao je na dostatnost procesa ispiranja. Iako su svi slojevi pokazali strukturnu homogenost, razlike u koncentraciji fitinske kiseline i vremenu umreživanja dovele su do razlike u mehanizmima rasta i posljedično u morfologiji presjeka tankih filmova. Ispitivanjem fizikalnih svojstava pri fiziološkim uvjetima potvrđena je stabilnost tankih filmova koji su maksimalni kapacitet apsorpcije postigli unutar tri sata.Thin films are being investigated as drug delivery systems, particularly for chemotherapeutic agents. Their application as implant coatings or standalone drug delivery systems enables controlled and targeted release of chemotherapeutics directly at the tumor site, thereby potentially reducing systemic toxicity and enhancing therapeutic efficacy. Phytic acid, a natural antioxidant, has been recognized for its role in the prevention and treatment of various pathological conditions and cancers. However, the development of suitable delivery systems is required to realize its full therapeutic potential. Due to its high density of hydroxyl groups, phytic acid has the capacity to form stable complexes with natural polymers, which can serve as carriers for its delivery. The biodegradability, biocompatibility, antimicrobial properties, and stability of chitosan–alginate (CA) polyelectrolyte complexes make them suitable for biomedical applications. Physical cross-linking of CA polyelectrolyte complexes with phytic acid may result in antitumor properties of the resulting materials. The aim of this study was to develop stable thin films based on chitosan–alginate polyelectrolyte complexes cross-linked with phytic acid using layer-by-layer assembly (LbL). The effect of phytic acid solution concentration (0.1, 0.5, and 1.0 wt%) and cross-linking time (3,5 and7 minutes) on the growth regime and properties of the resulting thin films was investigated. Thin films were characterized by ATR-FTIR spectroscopy to confirm cross-linking with phytic acid and to assess the effectiveness of the rinsing process after film preparation. Surface and cross-sectional morphology following fracture were examined using SEM analysis. The absorption capacity of the thin films was evaluated in phosphate buffer solutions (pH 6 and 8) and in phosphate-buffered saline (PBS, pH 7.4) over a period of 24 hours. ATR-FTIR spectroscopy confirmed successful cross-linking of the CA polyelectrolyte complex with phytic acid, and the absence of solvent absorption bands indicated the adequacy of the rinsing process. While all films exhibited structural homogeneity, variations in phytic acid concentration and cross-linking time resulted in differences in growth mechanisms, thereby affecting the morphology of the film cross-sections. Evaluation of film physical properties under physiological conditions confirmed their stability, with maximum apsorption capacity reached within three hours
Development of a method for the determination of ritlecitinib in blood plasma using LC/QToF technique
No full textAlopecija areata kronična je autoimuna bolest koja uzrokuje gubitak kose. Do nedavno dostupni tretmani i lijekovi u terapiji alopecije areate pokazivali su ograničenu učinkovitost i visok rizik od nuspojava. Razjašnjenje molekularnih mehanizama uključenih u patogenezu alopecije areate omogućilo je razvoj lijekova s novim mehanizmima djelovanja. Godine 2023. odobren je ritlecitinib, selektivni inhibitor JAK3 i TEC kinaza, za liječenje odraslih i adolescenata starijih od 12 godina u dozi od 50 mg jedanput dnevno. Ritlecitinib, kao ciljani lijek koji pokazuje klinički značajnu učinkovitost, predstavlja veliki iskorak u terapiji AA. U ovom radu predložena je bioanalitička metoda za određivanje ritlecitiniba u plazmi. Primjenom ekstrakcije čvrstom fazom s inovativnim sorbensima za pripremu biološkog uzorka te tekućinske kromatografije visoke djelotvornosti u sprezi s tandemskom masenom spektrometrijom s Q-ToF analizatorom za analizu uzorka, razvijena je metoda koja omogućuje pouzdano određivanje ritlecitiniba. Postignut je širok linearni raspon kvantifikacije pri iznimno niskim koncentracijama od 10 ng/mL do 2000 ng/mL.Alopecia areata is a chronic autoimmune disease that causes hair loss. Formerly available treatments and drugs for alopecia areata therapy showed limited effectiveness and a high risk of side effects. Understanding the molecular mechanisms involved in the pathogenesis of alopecia areata has enabled the development of drugs with new mechanisms of action. In 2023, ritlecitinib, a selective inhibitor of JAK3 and TEC kinases, was approved for the treatment of adults and adolescents over 12 years old at a dose of 50 mg once daily. Ritlecitinib, as a targeted drug demonstrating clinically significant efficacy, represents a major breakthrough in AA therapy. This paper proposes a bioanalytical method for the determination of ritlecitinib in blood plasma. By applying solid-phase extraction with innovative sorbents for biological sample preparation and high-performance liquid chromatography coupled with tandem mass spectrometry using a Q-ToF analyzer for sample analysis, a method was developed that enables reliable quantification of ritlecitinib. A wide linear quantification range was achieved at extremely low concentrations from 10 ng/mL to 2000 ng/mL
Development and validation of the HPLC-DAD-FLD method for the analysis of alpelisib in human plasma
No full textRak dojke predstavlja značajan javnozdravstveni problem zbog svojeg utjecaja na živote brojnih žena širom svijeta. U posljednjih
nekoliko godina, značajan napredak postignut je u liječenju raka dojke pozitivnog na hormonski receptor i negativnog na HER2 s
PIK3CA mutacijom korištenjem kombinacije alpelisiba s drugim lijekovima kao što su fulvestrant ili anastrozol. Alpelisib, inhibitor
PI3K-a, pokazuje velik potencijal u uspješnom liječenju ove vrste raka dojke, ali optimalni ishodi liječenja zahtijevaju učinkovito
praćenje terapije. U svrhu ovog rada razvijena je i validirana HPLC-DAD-FLD metoda za analizu alpelisiba u ljudskoj plazmi. Uzorci plazme pripremljeni su jednostavnom metodom taloženja proteina pomoću organskog otapala, što je osiguralo čistu analitnu matricu pogodnu za daljnju analizu. Korištena je kolona Phenomenex Gemini C18, dimenzija 150 × 4,6 mm i veličine čestica stacionarne faze 5 µm pri konstantnoj temperaturi od 25 °C. U razvijenoj metodi korištena je gradijentna eluacija mobilnom fazom koja se sastoji od 0,1 % mravlje kiseline u vodi i 0,1 % mravlje kiseline u metanolu. Brzina protoka iznosila je 1 mL/min. Korišteni su UV-Vis detektor i fluorescencijski detektor. Validacija metode provedena je ispitivanjem parametara linearnosti, točnosti, preciznosti i utjecaja matrice. Metoda je pokazala zadovoljavajuću linearnost unutar raspona koncentracija od 300 do 3000 ng/mL (r za DAD iznosi 0,99755, a za FLD 0,99664), visoku točnost (sve dobivene koncentracije čine od -1,8 do 11,3 % stvarne vrijednosti) i preciznost (RSD vrijednosti iznose od 1,1 do 4,3 %), te minimalan utjecaj matriksa (Meff se kreće od 95,8 do 106,1 %), čime je potvrđena njezina pouzdanost za analizu alpelisiba u kliničkim uzorcima. Konačno, razvijena i validirana metoda primijenjena je za analizu alpelisiba u plazmi tri pacijentice od kojih su rezultati za dvije pacijentice unutar validiranog raspona metode, a kod treće pacijentice alpelisib nije bilo moguće detektirati. Postoji mogućnost da pacijentica nije bila adherentna ili da je koncentracija u plazmi bila preniska da bi se ovom metodom mogla detektirati. Također je moguće da postoje interindividualne varijabilnosti koje utječu na koncentraciju alpelisiba u plazmi. Razvijena HPLC-DAD-FLD metoda za analizu alpelisiba u ljudskoj plazmi predstavlja napredak u mogućnostima praćenja terapije kod pacijentica s rakom dojke. Ova metoda može se koristiti za daljnja ispitivanja farmakokinetike alpelisiba, kao i za personalizaciju liječenja na temelju interindividualnih varijabilnosti među pacijenticama. Time se može postići bolja prilagodba terapije individualnim potrebama pacijentica, što će u konačnici rezultirati poboljšanjem ishoda liječenja i kvalitete života pacijentica oboljelih od raka dojke.Breast cancer represents a significant public health problem due to its impact on the lives of numerous women worldwide. In recent years, significant progress has been made in the treatment of hormone receptor-positive and HER2-negative breast cancer with PIK3CA mutation using a combination of alpelisib with other drugs such as fulvestrant or anastrozole. Alpelisib, a PI3K inhibitor, shows great potential in successfully treating this type of breast cancer, but optimal treatment outcomes require effective therapymonitoring. For the purpose of this study, an HPLC-DAD-FLD method was developed and validated for the analysis of alpelisib in human plasma. Plasma samples were prepared using a simple protein precipitation method with an organic solvent, ensuring a clean analytical matrix suitable for further analysis. A Phenomenex Gemini C18 column, dimensions 150 × 4.6 mm and particle size 5 µm, was used at a constant temperature of 25 °C. The developed method employed gradient elution with a mobile phase consisting of 0.1% formic acid in water and 0.1% formic acid in methanol. The flow rate was 1 mL/min. Both UV-Vis and fluorescence detectors were used. Method validation was carried out by examining parameters of linearity, accuracy, precision, and matrix effect. The method demonstrated satisfactory linearity within the concentration range of 300 to 3000 ng/mL (with an r value of 0.99755 for DAD
and 0.99664 for FLD), high accuracy (all obtained concentrations range from -1.8 to 11.3% of the true value) and precision (RSD values range from 1.1 to 4.3%), and minimal matrix effect (Meff ranges from 95.8 to 106.1%), confirming its reliability for the analysis of alpelisib in clinical samples.Finally, the developed and validated method was applied to analyze alpelisib in the plasma of three patients. The results for two patients were within the validated range of the method, while alpelisib could not be detected in the third patient's plasma. It is possible that the patient was not adherent to the therapy or that the plasma concentration was too low to be detected by this method. Additionally, inter-individual variability may affect the concentration of alpelisib in plasma.The developed HPLC-DAD-FLD method for analyzing alpelisib in human plasma represents an advancement in the capabilities of therapy monitoring for breast cancer patients. This method can be used for further pharmacokinetic studies of alpelisib and for the personalization of treatment based on inter-individual variability among patients. This approach can lead to better adjustment of therapy to the individual needs of patients, ultimately resulting in improved treatment outcomes and quality of life for breast cancer patients