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Polymeric particles for targeted anti-inflammatory therapy
Santarius, Karolina ; Holas, Ondřej (advisor) ; Smékalová, Monika (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, PhD. Consultant: Mgr. Barbora Boltnarová Student: Karolina Santarius Title of thesis: Polymeric particles for targeted anti-inflammatory therapy Macrophages are heterogenous population of cells, that play crucial role in inflammatory diseases like NASH. It was found that liver macrophages polarization into phenotype M1 is major factor in NASH progression. It seems that induced conversion from proinflammatory macrophages into anti-inflammatory is one of the potencial therapeutic target. This macrophages polarization can be achieved by drug delivery system based on drug-loaded nanoparticles. The aim of this work was to prepare and optimize the preparation of nanoparticles formulation based on polymeric nanoparticles loaded dexamethasone as model substance. The nanoparticles formulation was prepared by nanoprecipitation method using three PLGA polymers with different lactic/glycolic acid ratios. Several surfactants in various concentrations were used to optimize preparation. Prepared dexamethasone-loaded nanoparticles were characterized in terms of their size and polydisperzity index using dynamic light scattering. Zeta potencial of nanoparticles was determine by...
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Polymeric particles for targeted and enhanced bioavailability
Kozáčková, Daniela ; Holas, Ondřej (advisor) ; Svačinová, Petra (referee)
7 ABSTRACT Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, Ph.D. Consultant: Mgr. Barbora Boltnarová Student: Daniela Kozáčková Title of thesis: Polymeric particles for targeted and enhanced bioavailability Nanoparticles prepared from biodegradable and biocompatible polymers are useful for targeted therapy of inflammatory diseases and increase the bioavailability of poorly water-soluble anti-inflammatory drugs. Targeted distribution is mainly mediated by the physico-chemical properties of nanoparticles. This can reduce unwanted side effects of encapsulated drug. The ideal properties of nanoparticles for passive targeting to cells of the mononuclear phagocytic system (MPS) are size in the range of 100 nm to 300 nm, hydrophobic character and negative surface charge. Matrix-type polymeric nanoparticles were prepared. Prepared nanoparticles were evaluated for size, polydispersity index, zetapotential and encapsulation efficiency of the drug. Three anti-inflammatory substances with different water solubility - a dexamethasone, a dexamethasone acetate and a curcumin were encapsulated. The matrix of nanoparticles was made of PLGA copolymer, three types of PLGA with different lactide:glycolide ratio were used. Nanoparticles...
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Rheological properties of agar-based gels for ultrasound brain phantom
Schneiderová, Marie ; Šnejdrová, Eva (advisor) ; Holas, Ondřej (referee)
CHARLES UNIVERSITY FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY Author: Marie Schneiderová Supervisor: Phar Dr Eva nejdrová Ph D Title of diploma thesis: Rheological properties of agar-based gels for ultrasound brain phantom The diploma thesis deals with the evaluation of the rheological properties of agar gels on a rotational rheometer. The theoretical section contains the characterization of gels, their distribution, properties and use in pharmacy, describes agar and its characteristic properties. It also provides brief information on phantoms and describes the agar-based phantom in more detail. The principles of oscillation tests and their evaluation are described. Twelve gels with different agar concentrations were tested: a series of gels without glycerol and a series of gels with glycerol. The structure of the gels was characterized by the test Evaluating product texture using oscillatory testing and te perature stability in the range of 20 ř C to 40 ř C by the Single frequency strain controlled temperature ramp test. The viscoelastic properties of pig brain tissue were characterized by the same tests. The gel structure was confirmed in all samples tested. The stiffness expressed by the value of the complex modulus G * increases with the agar concentration....
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Effect of the generation of amino-decorated polyamidoamine dendrimers with ethylenediamine core at the (trans)dermal delivery of 5-fluorouracil
Houšková, Denisa ; Paraskevopoulos, Georgios (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Mgr. Anna Nová ková Author: Denisa Houšková Title of thesis: Effect of the generation of amino-decorated polyamidoamine dendrimers with ethylenediamine core at the (trans)dermal delivery of 5-fluorouracil. Dendrimers can be defined like highly branched, star-shaped macromolecules with nanometer-scale dimensions and unlimited applications in both biological and materials sciences. Polyamidoamine (PAMAM) dendrimers have been used to effectively enhance the (trans)dermal drug delivery of several active substances. Inspired by the structure of PAMAM dendrimers, a new class of dendrimers was designed having amino-functionalized periphery and ethylenediamine core. A repeating motif of bis(2-aminoethyl)glycine was used for generation growth up to the third generation. The new dendritic molecules of zero, first, second and third generation were tested for their ability to enhance the deposition of 5-fluorouracil in the different layers of human skin ex vivo by using Franz diffusion cells. The results suggest that the new dendrimers, at a concentration of 20 mg/mL in 60 % propylene glycol in water as vehicle, are able to deliver 5-fluorouracil at the...
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Formulation and (trans)dermal delivery of imiquimod
Hladký, Pavel ; Švecová, Barbora (advisor) ; Holas, Ondřej (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate: Pavel Hladký Consultant: PharmDr. Barbora Švecová, Ph.D. Title of Thesis: Formulation and (trans)dermal application of imiquimod Imiquimod (IMQ) is an active pharmaceutical substance which belongs to the group of heterocyclic imidazoquinolines. The mechanism of its effect is an induction of cellular immune response after topical administration, that is used for a treatment of tumors or viral diseases of the skin. In the Czech Republic it is available like a cream called Aldara® , the content of IMQ is 5 %. Although Aldara® is an effective medicine, many problems are associated with its use, especially high price, undesirable effects, disposable use, environmental pollution, etc. The aim of this work was to prepare new liposomes for topical administration containing lower ammount of IMQ (0.5 %) and evaluation of penetration of IMQ into human skin in vitro. To improve the entrance of the drug into the skin transdermal penetration enhancers were used. Permeation experiments were performed in Franz diffusion cells on human skin under conditions as close as possible to the physiological environment of the organism. Subsequently, the individual layers of the skin (stratum corneum, the epidermis,...
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Lipid based nanoparticles: drug delivery platform
Voldřichová, Lenka ; Holas, Ondřej (advisor) ; Svačinová, Petra (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Consultant: Mgr. Jana Kubačková Student: Lenka Voldřichová Title of thesis: Lipid based nanoparticles: drug delivery platform Lipic nanoparticles, as newly developed dosage forms, can overcome many drawbacks of conventional dosage forms. Their potential can be utilized in particular for prolonged, controlled and targeted release. They can also increase the bioavailability of drugs, especially those with poor solubility and also allow targeting, which causes increased accumulation of lipid nanoparticles in certain tissues compared to other tissues. nanoparticles suitable for drug encapsulation. The particles were prepared by the emulsion evaporation method. Their characterization was performed using a Zetasizer, which measured the particle size and the zeta potential. The properties of the formulations were evaluated in terms of nanoparticle size, polydispersity, zeta potential, and formulation properties. Differencial scanning calorimetry analysis was also performed on selected formulations. The selected final formulation was composed of 25 mg glycerol monostearate, 10 mg isopropyl myristate, 15 mg lecithin and Kolliphor P188 0,1% solution....
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The relationship between structure and activity of potential reactivators of acetylcholinesterase I.
Holas, Ondřej ; Opletalová, Veronika (advisor) ; Pohanka, Miroslav (referee)
The realtionship between structure and activity of potencial reactivators of acetylcholinesterase Organophosphorus compounds (OPC) are used as agricultural pesticides and in industry as fire retardants or plastificators. For military use there have been developed nerv agents (NA, e.g. tabun, sarin, somna, VX). The toxicity of these compounds is based upon phosphorylation or phosphonylation at the serine hydroxy group (Ser200) of the active site of the acetylcholinesterase. The current standard treatment consists of administration oxime reactivators in combination with anticholinergic drug (preferably atropin). Unfortunately, none from the currently used oximes is sufficiently effective against all types of the OPCs. The aim of this study is determination of the relationship between structure and activity of new reactivators against paraoxon inhibited AChE in vitro and comparison with currently available substances. For evaluation of reactivation activity has been chosen standard in vitro test using rat brain homogenate
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Nanofiltration
Heidrová, Hana ; Kučera, Radim (advisor) ; Holas, Ondřej (referee)
Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Nanofiltration Diploma thesis Candidate: Hana Heidrová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Consultant: PharmDr. Tomáš Holas, Ph.D. Nanofiltration is a pressure-driven membrane process which is characterized by using semipermeable membranes with approximately 1 nm pores. This method is used abundantly for the separation of substances with low molecular weight. It is used for example in the process of product isolation in pharmaceutical industry. This diploma thesis is focused on the description of the behaviour of three commercially produced nanofiltration membranes and also on testing of their potential use in the production of ergot alkaloids. The theoretical part is focused especially on the description of pressure-driven membrane processes, the use of nanofiltration in various areas and also on current and historical use of ergot alkaloids in therapy and on the description of their properties. The practical part is oriented particularly on examination of effect of various experimental parameters on the retention of selected ergot alkaloids (primarily of lysergic and isolysergic acid). The results are compared and critically analysed. Keywords: pressure-driven...
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Lipid based nanoparticles: drug delivery platform
Voldřichová, Lenka ; Holas, Ondřej (advisor) ; Svačinová, Petra (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, Ph.D. Consultant: Mgr. Jana Kubačková Student: Lenka Voldřichová Title of thesis: Lipid based nanoparticles: drug delivery platform Lipic nanoparticles, as newly developed dosage forms, can overcome many drawbacks of conventional dosage forms. Their potential can be utilized in particular for prolonged, controlled and targeted release. They can also increase the bioavailability of drugs, especially those with poor solubility and also allow targeting, which causes increased accumulation of lipid nanoparticles in certain tissues compared to other tissues. nanoparticles suitable for drug encapsulation. The particles were prepared by the emulsion evaporation method. Their characterization was performed using a Zetasizer, which measured the particle size and the zeta potential. The properties of the formulations were evaluated in terms of nanoparticle size, polydispersity, zeta potential, and formulation properties. Differencial scanning calorimetry analysis was also performed on selected formulations. The selected final formulation was composed of 25 mg glycerol monostearate, 10 mg isopropyl myristate, 15 mg lecithin and Kolliphor P188 0,1% solution....
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Rheological behavior of branched polyesters
Martiška, Juraj ; Šnejdrová, Eva (advisor) ; Holas, Ondřej (referee)
CHARLES UNIVERSITY IN PRAGUE Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical technology Name: Juraj Martiska Title of diploma thesis: Rheological behavior of branched polyesters Supervisor: PharmDr. Eva Snejdrova, Ph.D. This thesis studies rheological and thermal properties of potencial polyester drug carrier composed of an equimolar proportion of D,L-lactic and glycolic acids, branched with tripentaerythritol at a concentration of 3%, and its analogs plasticized with methyl salicylate at different concentrations. The theoretical part deals with the characterization of polymers, their plasticizing and rotational rheometry. In the experimental part were prepared plasticized polyesters then were determined their glass transition temperatures using a DSC, and on rotational rheometer was tested their rheological behavior. According to the results of thermal analysis, methyl salicylate significantly lowers the glass transition temperature of the tested polyester and seems to be suitable plasticizer. The resulting data of rheological analyzes show that 3T plasticized polymer exhibits pseudoplastic behavior at 25řC and concentration of methyl salicylate 20% when the viscosity is highest. Viscosity of polymer systems significantly decreases with increasing temperature and concentration...
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