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Synthesis and use of organic biodegradable aerogels as drug carriers
Anja Veronovski, Zoran Novak, Željko Knez, 2012, original scientific article

Abstract: Aerogels of natural polysaccharides possess both biocharacteristics of polysaccharides, such as good biological compatibility and cell or enzyme-controlled degradability, and aerogel characteristics, such as very high porosity and specific surface areas that makes them highly attractive in drug delivery. Biodegradable alginate aerogels were synthesized via a sol-gel process. In the present work two methods of ionic cross-linking were used to prepare alginate hydrogels as monoliths and spheres, which can be further easily converted to high surface area aerogels. The aerogels obtained were further used as drug carriers. We investigated the effect of process parameters, such as starting concentration and viscosity of alginate solution, on synthesis products and on model drug (nicotinic acid) release. The results indicate that by using the internal setting cross-linking method for obtaining monolithic aerogels nicotinic acid was released in a more controlled manner. The aerogels thus obtained also exhibited smaller volume shrinkage than the ones described in other publications. However, with increasing alginate concentration in both types of synthesis more compact and cross-linked aerogels were formed.
Keywords: organic biodegradable gels, natural polysaccharides, aerogels, drug cariers
Published: 01.06.2012; Views: 1410; Downloads: 84
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Antimicrobial medical textiles based on chitosan nanoparticles for gynaecological treatment
Tijana Ristić, 2014, doctoral dissertation

Abstract: The aim of this dissertation was to develop a novel medical tampon for alternative gynaecological treatment using chitosan nanoparticles as an antimicrobial agent or as a drug delivery system. For this purpose viscose tampon band was used and functionalized with chitosan and trimethyl chitosan nanoparticles. A comprehensive of interactions between chitosan and cellulose as well as characterization of prepared materials were done. At the beginning, chitosan (CS) and trimethyl chitosan (TMC) solutions, as well as nanoparticles synthesised by ionic gelation were studied. Their characterization was focused on determining the charge and antimicrobial properties against common pathogenic microorganism. The influence of cationic charge on the inhibition of microbial growth was confirmed. Since CS and TMC solutions and nanoparticles dispersions exhibited antibacterial activity against Lactobacillus, a detailed investigation in chitosan’s antimicrobial mode of action was performed using a novel diffusion nuclear magnetic resonance (D-NMR). D-NMR allowed the monitoring of intra- and extracellular water exchange from the cells indicating the membrane alteration and leakage of intracellular constituencies. Further, in order to study the adsorption phenomena and molecular interactions between CS/TMC (solution or nanoparticles) and cellulose material, model cellulose surfaces were used, and adsorption was studied by quartz crystal microbalance with dissipation. CS and TMC were favourably deposited onto cellulose model surface at higher ionic strength, higher pH values, i.e. factors causing lower solubility, where the presence of electrostatic interactions was negligible and non-electrostatic interactions were dominant. The knowledge gained from the model surfaces was extremely helpful in characterization of real systems, i.e. functionalized cellulose fibres and for understanding the obtained results. Immobilization of CS and TMC (in the form of solution and/or nanoparticles) onto cellulose viscose fibres was confirmed with several analytical methods. The attachment of chitosan onto fibres was reversible, as endorsed with desorption studies mimicking the conditions of vaginal usage. Evaluation of antimicrobial properties was performed using two different techniques, both revealing a high inhibition of the tested microorganism. In addition, Lactobacillus susceptibility testing has shown that chitosan-coated fibres do not have any negative influence on the resident microbiota. Assessment of in-vitro cytotoxicity demonstrated that samples do not cause a cytotoxic effect in direct contact. Additionally, model drug was incorporated into chitosan nanoparticles and subsequently attached onto fibres in order to create modern, vaginal drug delivery systems. Antimicrobial medical textiles investigated in the scope of this dissertation show the potential for their exploitation in gynaecological field as preventive or curative treatment without triggering any adverse effects for the user.
Keywords: chitosan, N, N, N-trimethyl chitosan, nanoparticles, antimicrobial activity, cellulose model films, regenerated cellulose fibres, diffusion nuclear magnetic resonance, quartz crystal microbalance, vaginal infections, drug delivery systems, cytotoxicity
Published: 13.02.2014; Views: 2299; Downloads: 100
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Interakcije zdravil z zaviralci angiotenzinske konvertaze
Marjetka Pal, Polonca Ferk, 2012, review article

Abstract: V članku predstavljamo pregled potencialno klinično pomembnih interakcij zdravil (DDIs) z zaviralci angiotenzinske konvertaze (ACE). Na osnovi pregleda dveh knjig Stockleyʼs Drug Interactions in dveh preko spleta dostopnih podatkovnih zbirk o DDIs smo opisali več kot deset takih DDIs, razložili njihove mehanizme, opredelili njihov klinični pomen ter navedli možnosti za njihovo preprečevanje oz. ustrezno obravnavo. Večina DDIs z zaviralci ACE je farmakodinamičnih, le nekaj jih je na nivoju farmakokinetike. Največ DDIs z zaviralci ACE se odraža kot prekomerno znižanje krvnega tlaka, hiperkaliemija ali nefrotoksičnost. Dokazali so tudi, da zaviralci ACE zvečajo toksičnost litija in da lahko vplivajo na pojav hudih preobčutljivostnih reakcij pri bolnikih, ki so prejeli parenteralne pripravke železa, ali pri bolnikih, ki sočasno jemljejo alopurinol. Prav tako je zaviralce ACE zaradi njihove lastne hepatotoksičnosti potrebno previdno kombinirati z drugimi hepatoksičnimi zdravili. Zaradi velike porabe zaviralcev ACE je pogostost neželenih učinkov zdravil zaradi DDIs z zaviralci ACE visoka. Ugodno pa je, da lahko v večini primerov teh DDIs ustrezno ukrepamo že s primernim kliničnim in laboratorijskim spremljanjem bolnikov oz. s prilagoditvijo odmerkov sočasno predpisanih zdravil.
Keywords: angiotensin-converting enzyme inhibitors, drug-drug interactions, drug-interaction databases
Published: 10.07.2015; Views: 1337; Downloads: 47
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Nevtropenični enterocolitis, povzročen s tirostatikom - poročilo o primeru
Nina Kobilica, Marjan Skalicky, Andrej Bergauer, Vojko Flis, 2010, professional article

Abstract: Nevtropenični enterocolitis, povzročen s tirostatikom
Keywords: neutropenic enterocolitis, adverse drug reactions, antithyroid drugs, surgery
Published: 10.07.2015; Views: 1039; Downloads: 17
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Formation, characterization and application of polysaccharide aerogels
Gabrijela Horvat, 2018, doctoral dissertation

Abstract: The aim of this PhD dissertation was to describe and analyze the preparation and characterization of polysaccharide aerogels and their future pharmaceutical and medical application. For the research, we used four types of polysaccharides: pectin, alginate, xanthan and guar. We used two types of pectin, high-methoxyl and low-methoxyl pectin, because of their different gelation mechanisms. The first part of the dissertation describes the preparation and characterization of pure polysaccharide aerogels. First, we prepared pectin spherical aerogels, cross-linked with three different ions, and we investigated their final properties. Later, we developed a new method for the preparation of alginate, pectin, xanthan and guar aerogels. We used only ethanol and no other cross-linkers. Ethanol was removed in the later processes of supercritical drying, and the remaining final material was thus only porous polysaccharide. By this method, we were able to prepare pure xanthan and guar aerogels. Prior to this study, xanthan and guar aerogels were prepared only as composites. Pectin aerogels prepared by the new method have amazing properties. On the other hand, alginate aerogels show poor characteristics, and thus the methods need to be optimised. We tried different alginate viscosities, different alcohols (methanol, ethanol, 1-propanol and 1-butanol), and we investigated longer (24h) and shorter (1h) gel setting times. The second part of this dissertation describes the pharmaceutical and medical applications of prepared aerogels. The release of diclofenac sodium from spherical pectin aerogels was investigated in vitro. Calcium cross-linked aerogels were not able to retain the drug, and its release was immediate. In order to achieve controlled release of diclofenac sodium, zinc ions had to be used as cross-linkers. Later, a low water-soluble drug, nifedipine, was used as a model drug for the monolithic aerogels prepared by the new method. The release of nifedipine from pectin and alginate aerogels was highly increased, compared to the crystalline drug. This result is promising for future evaluation of these materials for increasing the bioavailability of poorly water-soluble drugs. Nifedipine release from xanthan and guar aerogels was prolonged up to two weeks. This result reveals a new perspective on such materials for their potential use in medicine as implants and local drug delivery. According to these results, we then developed a new coating material for medical-grade stainless steel from xanthan and pectin. An aerogel coating was loaded with diclofenac sodium and indomethacin, and their release profiles were investigated in vitro. Electrochemical analysis and cell tests proved the safety of such materials for use in medicine. Using aerogel coatings, the drug can be introduced locally into the body; therefore, the need for intravenous, post-operational treatment is greatly reduced.
Keywords: polysaccharides, aerogels, supercritical drying, drug carriers
Published: 09.04.2018; Views: 785; Downloads: 171
.pdf Full text (5,84 MB)

Scaffold hopping and bioisosteric replacements based on binding site alignments
Samo Lešnik, Janez Konc, Dušanka Janežič, 2016, original scientific article

Abstract: Bioisosteric replacements and scaffold hopping play an important role in modern drug discovery and design, as they enable the change of either a core scaffold or substitutes in a drug structure, thereby facilitating optimization of pharmacokinetic properties and patenting, while the drug retains its activity. A new knowledge-based method was developed to obtain bioisosteric or scaffold replacements based on the extensive data existing in the Protein Data Bank. The method uses all-against-all ProBiS-based protein superimposition to identify ligand fragments that overlap in similar binding sites and could therefore be considered as bioisosteric replacements. The method was demonstrated on a specific example of drug candidate – a nanomolar butyrylcholinesterase inhibitor, on which bioisosteric replacements of the three ring fragments were performed. The new molecule containing bioisosteric replacements was evaluated virtually using AutoDock Vina; a similar score for the original and the compound with replacements was obtained, suggesting that the newly designed bioisostere compound might retain the potency of the original inhibitor.
Keywords: bioisosteres, scaffold hopping, protein alignment, ProBiS, drug design, analysis methods, matter structure, modelling
Published: 05.07.2017; Views: 523; Downloads: 259
.pdf Full text (2,30 MB)
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Analyzing information seeking and drug-safety alert response by health care professionals as ew methods for surveillance
Alison Callahan, Igor Pernek, Gregor Štiglic, Jurij Leskovec, Howard Strasberg, Nigam Haresh Shah, 2015, original scientific article

Abstract: Background: Patterns in general consumer online search logs have been used to monitor health conditions and to predict health-related activities, but the multiple contexts within which consumers perform online searches make significant associations difficult to interpret. Physician information-seeking behavior has typically been analyzed through survey-based approaches and literature reviews. Activity logs from health care professionals using online medical information resources are thus a valuable yet relatively untapped resource for large-scale medical surveillance. Objective: To analyze health care professionals% information-seeking behavior and assess the feasibility of measuring drug-safety alert response from the usage logs of an online medical information resource. Methods: Using two years (2011-2012) of usage logs from UpToDate, we measured the volume of searches related to medical conditions with significant burden in the United States, as well as the seasonal distribution of those searches. We quantified the relationship between searches and resulting page views. Using a large collection of online mainstream media articles and Web log posts we also characterized the uptake of a Food and Drug Administration (FDA) alert via changes in UpToDate search activity compared with general online media activity related to the subject of the alert. Results: Diseases and symptoms dominate UpToDate searches. Some searches result in page views of only short duration, while others consistently result in longer-than-average page views. The response to an FDA alert for Celexa, characterized by a change in UpToDate search activity, differed considerably from general online media activity. Changes in search activity appeared later and persisted longer in UpToDate logs. The volume of searches and page view durations related to Celexa before the alert also differed from those after the alert. Conclusions: Understanding the information-seeking behavior associated with online evidence sources can offer insight into the information needs of health professionals and enable large-scale medical surveillance. Our Web log mining approach has the potential to monitor responses to FDA alerts at a national level. Our findings can also inform the design and content of evidence-based medical information resources such as UpToDate
Keywords: internet log analysis, data mining, physicians, information-seeking behavior, drug safety surveillance
Published: 02.08.2017; Views: 768; Downloads: 95
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