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Preparation and evaluation of nanoparticles for targeted treatment of inflammatory diseases
Wurzel, Natalie ; Holas, Ondřej (advisor) ; Smékalová, Monika (referee)
Charles University, Faculty of Pharmacy in Hradci Králové Department of Pharmaceutical Technology Supervisor: PharmDr. Ondřej Holas, PhD Consultant: Mgr. Barbora Boltnarová Student: Natalie Wurzel Title of Thesis: Preparation and evaluation of nanoparticles for targeted treatment of inflammatory diseases Nanoparticles are used in the health sciences for, among other things, targeted drug delivery. This is used for the therapy of cancer and chronic inflammatory diseases. The aim of this diploma thesis was to prepare nanoparticles suitable for targeted treatment of inflammatory diseases. The task was to determine the ideal concentration of the active substance, which would ensure high encapsulation efficiency and drug loading. The difference between nanoparticles prepared from PLGA 5/5E and PLGA 7/3A was also investigated. Nanoparticles were prepared by the nanoprecipitation method. The matrix of the nanoparticles was composed of PLGA with different ratios of lactic acid and glycolic acid. Acetone was used as the organic solvent. The encapsulated active substance was the anti-inflammatory dexamethasone acetate. The aqueous phase was consisted of a 0.1% aqueous solution of Pluronic F-127. The evaluated parameters of the resulting nanoparticles included size, polydispersity index, zeta potential,...
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Polymeric nanoparticles: platform for poorly water soluble drugs delivery
Roztočilová, Adéla ; Holas, Ondřej (advisor) ; Svačinová, Petra (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, Ph.D. Student: Adéla Roztočilová Title of thesis: Polymeric nanoparticles as a platform for delivery of poorly water-soluble drugs Polymer nanoparticles can be used as drug carriers due to their beneficial properties. One of the advantages of polymeric nanoparticles is, for example, to increase the solubility of drugs in water. They have great potential in the therapy of inflammatory diseases such as Crohn's disease or in shifting cancer pharmacotherapy. The main objective of this thesis was to prepare polymeric nanoparticles with encapsulated curcumin as model active ingredient. Four types of poly(lactic-co-glycolic acid) (PLGA) copolymer were used to prepare the nanoparticles. Nanoprecipitation and emulsion evaporation methods were employed. The parameters evaluated were encapsulation efficiency, drug loading, particle size and polydispersity. Both the water phase, where two different surfactants were employed, and the organic phase were varied during the experiment. The experimental part also used a dissociation method where two types of PLGA copolymer were compared and during the dissociation, samples were taken at predetermined times to determine the total...
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Polymeric nanoparticles for poorly water soluble drugs delivery
Nekolová, Martina ; Holas, Ondřej (advisor) ; Smékalová, Monika (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Mentor: PharmDr. Ondřej Holas, Ph.D. Student: Martina Nekolová Title of thesis: Polymeric nanoparticles for poorly water-soluble drugs delivery Polymeric nanoparticles represent a modern drug form. One of the main advantages is influencing the pharmacokinetic properties of the administered substance - e.g. increasing solubility in water. They enable the targeted delivery of the drug to the affected tissue and this way minimize adverse effects. This could be of great benefit to the therapy of cancer or inflammatory diseases. Both the target tissue and the nanoparticles must have some specific properties. For particles, it is, for example, size and surface charge. The aim of this work was to prepare nanoparticles with a substance poorly soluble in water, represented by curcumin. The particles were prepared by the nanoprecipitation method with different types of poly(lactic-co-glycolic acid) (PLGA) copolymer. A 50:50 linear PLGA polymer and a branched PLGA A2 polymer were used. The prepared nanoparticles were compared on several parameters - particle size and polydispersity, encapsulation efficiency (EE), drug-loading capacity (DLC) and dissolution profile. PLGA 50:50 was found to provide...
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The effect of polymer microfibers on rheological and mechanical properties of calcium phosphate bone cements
Dzurov, Matej ; Montufar Jimenez, Edgar Benjamin (referee) ; Vojtová, Lucy (advisor)
Táto diplomová práca sa zaoberá mechanickými a reologickými vlastnosťami resorbovateľného polymér-fosforečnanového kompozitu na báze kostného cementu vystuženého mikrovláknami z PCL (poly(-kaprolaktón)) a Pluronic-om modifikovanými PCL vláknami. Teoretická časť popisuje štruktúru kostí, vývoj kostných cementov a štrukturálne prídavky (aditíva). V experimentálnej časti je rozoberaná syntéza a charakterizácia PLGA-PEG-PLGA termosenzitívneho kopolyméru a - modifikácie fosforečnanu vápenatého ako aj technika prípravy mikrovláken. Roztok kopolyméru bol použitý pre zlepšenie obmedzenej injektovateľnosti pasty s pomerom kvapalnej k práškovej fáze (L/P) 0,5 ml/g pre všetky vzorky. Dve rôzne techniky zamiešania pasty boli použité pre možnosť kontrolovania porozity pripraveného cementu. PCL a PCL-Pluronic vlákna využité ako výstuž boli testované v troch rôznych prídavkoch, a to 1, 3 a 5 hmotnostných percent vláken na celkovú hmotnosť pripravenej pasty. Pripravené pasty boli testované pomocou dynamickej reologickéj analýzy na reometri pri laboratórnej teplote (23 °C) a fyzologických podmienkach (37 °C) so zámerom stanoviť spracovateľnosť a tuhnutie pasty. Vzorkám na ostatok analýz bolo umožnené vytvrdzovanie pri fyziologických podmienkach po dobu 10 dní. Po vytvrdení boli testované mechanické parametre ako sú pevnosť v tlaku, Youngov modul pružnosti a pevnosť v ťahu v priemere vysušených a v niektorých prípadoch aj hydratovaných vzoriek. Porozita vzoriek bola stanovená pomocou Roentgénovej počítačovej mikro-tomografie. Rastrovacia elektrónová mikroskopia bola využitá na študovanie mikroštruktúry a zabudovanie vláken do keramickej matrice. Prítomnosť vláken bola semi-kvantitatívne stanovená pomocou Fourier transformovanej infračervenej spektroskopie. Difrakcia Roentgénového žiarenia poskytla údaje o fázovom prechode prášku a jeho mineralogickom zložení. Jednotlivé hodnoty, obdržané z jednotlivých analýz, boli medzi sebou porovnané a adekvátne diskutované. Výsledkom práce je potvrdenie mierneho zlepšenia pevnosti v tlaku vzoriek vystužených hydrofóbnymi PCL alebo amfifilnými PCL-Pluronic vláknami pričom, PCL-Pluronic vlákna poskytli lepšie výsledky. Preto bolo usúdené, že polymér-fosforečnanový kostný cement vystužený vláknami je nádejným kandidátom na uplatnenie v chirurgickej praxi.
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Modification of parameters of nanoparticles prepared from aliphatic hydroxyacids polyesters.
Křivková, Marie ; Dittrich, Milan (advisor) ; Šnejdrová, Eva (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Consultant: doc. RNDr. Milan Dittrich, CSc. Student: Marie Křivková Title of Thesis: Modification of parameters of nanoparticles prepared from aliphatic hydroxyacids polyesters Polyesters of aliphatic α-hydroxyacids are mentioned in the theoretical part. A significant part of it is mostly devoted to the polyester PLGA. Physicochemical properties, the process of biodegradation and biodistribution are described there. Subsequently, some examples of PLGA utilization in pharmacy and medicine are mentioned. The theoretical part deals also with the method of diffusion used for nanoparticles preparation, which was used in the experimental part, and the principles of size and surface charge measurements of these nanoparticles. The crucial part of this master thesis is based upon an experiment. It is focused on various approaches to the formulation of nanoparticles out of aliphatic polyester carriers with variable molecular constitution. Polymer PLGA with linear molecule and polymers containing PLGA branched on tripentaerythritol and polyacrylic acid were used. Using the diffusion method, nanoparticles were prepared out of these carriers. The outer water-based phase was modified by use of cetrimide of different...
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Preparation of pharmaceutical formulations based on polymeric and lipid carriers
Kubačková, Jana ; Zbytovská, Jarmila (advisor) ; Panáček, Aleš (referee) ; Štěpánek, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate Mgr. Jana Kubačková Supervisor Assoc. Prof. Jarmila Zbytovská, Mgr., Dr. rer. nat. Co-supervisor PharmDr. Ondřej Holas, PhD. Title of Doctoral Thesis Preparation of pharmaceutical formulations based on polymeric and lipid carriers Nanomedicine allows application of nanoscaled drug delivery carriers to achieve a therapy that can be tailored in terms of e.g. controlled release, site-specific delivery and protection of an active substance. From multiple nanoplatforms available for drug delivery, advantage was taken of biocompatible and biodegradable polymers and lipids to enable targeted intracellular delivery, delivery of a poorly water-soluble drug and delivery of a sensitive macromolecule. In the study with biodegradable polymeric nanomaterial we worked with experimental poly(lactic-co-glycolic acid) (PLGA) polymers. The formulations were optimised for targeting to phagocytic macrophages - of size up to 300 nm and negative surface charge. For this purpose, two linear and one branched PLGA were screened in combination with one of four surfactants in low concentrations (0.1-1%). These PLGA polymers were formulated into nanoparticles and loaded with a hydrophilic fluorescent dye Rhodamine B...
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Acidoresistant polymeric nanoparticles: preparation and assessment
Semrádová, Adélka ; Holas, Ondřej (advisor) ; Svačinová, Petra (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of: Pharmaceutical Technology Consultants: PharmDr. Ondřej Holas, Ph.D. Mgr. Jana Kubačková Student: Adélka Semrádová Title of thesis: Acidoresistant polymeric nanoparticles: preparation and assessment Use of oral drug delivery nanosystems has a great potential in therapy of inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Nanosized delivery systems are more efficiently accumulated at the inflammatory site, targeting specifically macrophages to resolve inflammation locally and reduce systemic adverse effects. The aim of this research was to prepare pharmaceutical formulations based on polymeric nanoparticles. Three types of poly(lactide-co-glycolide) - two linear and one branched polymer - together with the acidoresistant polymer cellulose-acetate phthalate (CAF) in various ratios were used to prepare nanoparticles by nanoprecipitation method. Rhodamine B was used as model active substance. The effect of acidoresistant component content on size and zeta potential of the nanoparticles was evaluated. Furthermore, dissolution tests were performed at both acidic and physiological pH. It was found that CAF doesn't have any significant effect on size of the particles and their stability....
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Preparation of pharmaceutical formulations based on polymeric and lipid carriers
Kubačková, Jana ; Zbytovská, Jarmila (advisor) ; Panáček, Aleš (referee) ; Štěpánek, František (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Candidate Mgr. Jana Kubačková Supervisor Assoc. Prof. Jarmila Zbytovská, Mgr., Dr. rer. nat. Co-supervisor PharmDr. Ondřej Holas, PhD. Title of Doctoral Thesis Preparation of pharmaceutical formulations based on polymeric and lipid carriers Nanomedicine allows application of nanoscaled drug delivery carriers to achieve a therapy that can be tailored in terms of e.g. controlled release, site-specific delivery and protection of an active substance. From multiple nanoplatforms available for drug delivery, advantage was taken of biocompatible and biodegradable polymers and lipids to enable targeted intracellular delivery, delivery of a poorly water-soluble drug and delivery of a sensitive macromolecule. In the study with biodegradable polymeric nanomaterial we worked with experimental poly(lactic-co-glycolic acid) (PLGA) polymers. The formulations were optimised for targeting to phagocytic macrophages - of size up to 300 nm and negative surface charge. For this purpose, two linear and one branched PLGA were screened in combination with one of four surfactants in low concentrations (0.1-1%). These PLGA polymers were formulated into nanoparticles and loaded with a hydrophilic fluorescent dye Rhodamine B...
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Materials For Biodegradable Bones Based On Fe
Hrabovský, Jan
The thesis deals with biodegradable bone implants which must have good mechanicalproperties and also good compatibility with the human body. The thesis contains literary research inthe area of bone physiology, biogenic materials and implants for the human body. The thesis focueson the selection of suitable materials for biogenic implants.
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