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The evaluation of the effect of PAMAM dendrimers in the solubility of lmiquimod
Micková, Thu Thao ; Paraskevopoulos, Georgios (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Eleni Panoutsopoulou Author: Mgr. Thu Thao Truongová Title of the thesis: The evaluation of the effect of PAMAM dendrimers in the solubility of Imiquimod Dendrimers are highly branched polymeric compounds with defined properties. They are used as a nanoparticle delivery system, however concurrently they have significant potential in enhancing the solubility of poorly water soluble drugs. Dendrimers work as drug carriers either by encapsulating the drug in their branched internal structure or they create interactions with the drug in the outer layer via terminal functional groups. The aim of this work was to evaluate the effect of polyamidoamine (PAMAM) dendrimers on the solubility of the hydrophobic drug imiquimod. Solutions of zero, first, second and third generation dendrimers were prepared at six different concentrations. During the experiment, the pH of the solutions was measured before and after addition of excess amount of imiquimod. Subsequently, analysis was performed by high-performance liquid chromatography. The measured results show that the first generation of PAMAM dendrimers is able to increase the solubility of imiquimod in...
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Interaction of PAMAM dendrimers with the human stratum corneum
Žofková, Kateřina ; Paraskevopoulou, Anna (advisor) ; Svačinová, Petra (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: PharmDr. Anna Paraskevopoulou, Ph.D. Author: Kateřina Žofková Title of the thesis: Interaction of PAMAM dendrimers with human stratum corneum Dendrimers are highly branched, monodisperse macromolecules. On the basis of the degree of branching, can be distinguished different generations of dendrimers that arise as the dendrimers expand. Higher generations of dendrimers form spherical structures with an internal cavity, where molecules such as a drug can be encapsulated. Due to their structure, which can be specifically and controllably modified, dendrimers are investigated for their use in biomedicine. One of the most widely used groups of dendrimers are polyamidoamine (PAMAM) dendrimers, based on an ethylenediamine core, branched amide and amine units, and terminal functional groups. PAMAM dendrimers with amine groups have proven useful in the past as skin penetration enhancers of different drugs. However, the mechanism how these molecules affect skin barrier function is not yet known. Therefore, in this work was investigated the mechanism of interaction of PAMAM dendrimers with lipids of stratum corneum (SC), the uppermost skin layer where the skin barrier is found. Second, third and...
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The effect of Ca2+cations and cholesteryl sulfate on the human skin barrier model
Kelemanová, Aneta ; Pullmannová, Petra (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Author: Aneta Kelemanová Supervisor: Mgr. Petra Pullmannová, Ph.D. Title of diploma thesis: The effect of Ca2+ cations and cholesteryl sulfate on the human skin barrier model The structure and composition of the outermost layer of the epidermis, the stratum corneum, form a skin barrier to transepidermal water loss. The main components of the stratum corneum are corneocytes and the intercellular lipid matrix. The intercellular lipid matrix is a mixture of ceramides, cholesterol, and free fatty acids. Cholesterol esters, such as cholesteryl sulfate, are also present. This unique lipid mixture forms a multilamellar layer with short and long crystalline phases with periodicities of approximately 6 and 13 nm. A separated cholesterol phase with a periodicity of about 3,4 nm can also be found in the stratum corneum. The most common lateral packing of the lipid mixture is orthorhombic. Hexagonal or fluid packing is less common. The aim of this diploma thesis was to optimize the conditions for spontaneous arrangement of the isolated human skin lipids in an aqueous medium with the addition of Ca2+ cations and cholesteryl sulfate. A human skin barrier model was created from the prepared lipid dispersion...
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Dissolution of a drug from thin films based on plasticized PLGA derivatives
Kodytková, Simona ; Šnejdrová, Eva (advisor) ; Paraskevopoulou, Anna (referee)
CHARLES UNIVERSITY Faculty od Pharmacy in Hradec Kralove Department od Pharmaceutical Technology Author: Simona Kodytková Title od Diploma thesis: Dissolution of a drug from thin films based on plasticized PLGA derivatives Supervisor: PharmDr. Eva Šnejdrová, Ph.D. The aim of the presented work was to formulate liquid systems for the formulation of in situ thin films (FFS) based on copolymers D,L-lactic and glycolic acid (PLGA) and to study the effect of a combination of salicylic acid and methyl salicylate in film and the effect of their various concentrations on dissolution profiles. The theoretical section summarizes the general knowledge about the characteristics, substances used to formulate FFS and methods for their testing. In the experimental section, liquid systems forming in situ films by solvent evaporation were prepared, based on a linear or branched PLGA polymer containing salicylic acid as a poor water soluble drug, and methyl-salicylate as a multifuctional plasticizer, at different concentrations. The solubility test of salicylic acid, methyl salicylate and their mixtures, and dissolution tests of drug and plasticizer in phosphate buffer buffer pH 5.5 at 37 řC were performed. Salicylate analysis was performed by HPLC. Based on the results, it can be stated that faster dissolution of...
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Active encapsulation of imiquimod in liposomes with dendrimers
Manna, Dina Faeq Mohd Said ; Paraskevopoulos, Georgios (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Eleni Panoutsopoulou Author: Dina Manna Title of the thesis: Active Encapsulation of Imiquimod in Liposomes with Dendrimers One of the main obstacles to tackle when dealing with drug delivery systems such as liposomes is efficiently loading adequate concentration of active ingredient. Drug encapsulation in liposomes occurs in two possible methods: passive and active loading. Passive drug loading involves the capture of drugs into the liposome whilst it is being prepared. Active loading however is the passage of drug through liposome's phospholipid bilayer after the liposome is fully formed. This method has been shown to be effective for low molecular weight ionizable active components and it was hypothesized to be an effective method of encapsulation of imiquimod. IMQ is an imidazole quinolone drug known for its extreme hydrophobicity and basicity and have been used for skin diseases (e.g. skin cancer). During our approach, liposomes were prepared using the classical thin layer method while the lipids were hydrated with aqueous solution of in-house synthesized first-generation dendrimer of two different concentrations (5 mM and 10 mM). Once...
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Study of Corneocyte Lipid Envelope
Hrdinová, Iva ; Kováčik, Andrej (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Author: Iva Hrdinová Supervisor: doc. PharmDr. Andrej Kováčik, Ph.D. Title of diploma thesis: Study of corneocyte lipid envelope The stratum corneum (SC) is the uppermost layer of the human epidermis. The structure of this layer is composed of corneocytes which are surrounded by a lipid matrix. Besides the free lipids (ceramides, free fatty acids, and cholesterol), there are covalently bound lipids called the corneocyte lipid envelope (CLE). While the role of free lipids is known, the effect of the CLE on the SC permeability is still unclear. In this work, we aimed to answer the question: "Is the CLE important in the skin permeability, and does the CLE play any role as a template for the free lipid arrangement in the SC?" A partial aim of this work was to develop a valid method for the preparation of the CLE models, including SC delipidation/relipidation procedures. We prepared the SC models from the human epidermis. First, we extracted the free lipids from SC with organic solvents, and then we saponified the extracted SC with alkaline methanol. The free lipids were then applied onto the extracted and saponified SC in an organic solvent under different temperature conditions (room temperature vs....
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The effect of Ca2+cations and cholesteryl sulfate on the human skin barrier model
Kelemanová, Aneta ; Pullmannová, Petra (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Author: Aneta Kelemanová Supervisor: Mgr. Petra Pullmannová, Ph.D. Title of diploma thesis: The effect of Ca2+ cations and cholesteryl sulfate on the human skin barrier model The structure and composition of the outermost layer of the epidermis, the stratum corneum, form a skin barrier to transepidermal water loss. The main components of the stratum corneum are corneocytes and the intercellular lipid matrix. The intercellular lipid matrix is a mixture of ceramides, cholesterol, and free fatty acids. Cholesterol esters, such as cholesteryl sulfate, are also present. This unique lipid mixture forms a multilamellar layer with short and long crystalline phases with periodicities of approximately 6 and 13 nm. A separated cholesterol phase with a periodicity of about 3,4 nm can also be found in the stratum corneum. The most common lateral packing of the lipid mixture is orthorhombic. Hexagonal or fluid packing is less common. The aim of this diploma thesis was to optimize the conditions for spontaneous arrangement of the isolated human skin lipids in an aqueous medium with the addition of Ca2+ cations and cholesteryl sulfate. A human skin barrier model was created from the prepared lipid dispersion...
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Formulation of Imiquimod loaded liposomes in the presence of dendrimers
Štěpničková, Tereza ; Paraskevopoulos, Georgios (advisor) ; Paraskevopoulou, Anna (referee)
Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Technology Supervisor: Dr. Georgios Paraskevopoulos, Ph.D. Consultant: Eleni Panoutsopoulou Author: Tereza Štěpničková Title of the thesis: Formulation of Imiquimod loaded liposomes in the presence of dendrimers Dendritic molecules, as highly branched polymers, are very attractive nanosystems for broad biomedical applications. Their specific properties include the ability to increase transdermal permeation of active ingredients as well as the ability to increase the water solubility of poorly soluble drugs. The main purpose of this thesis was the utilization of dendrimers to raise the concentration of the chemoterapeutic drug imiquimod inside liposomal formulations. Solutions of dendritic molecules zero, first, second and third generation were prepared, each at concentrations of 5 mg/ml and 10 mg/ml. These were subsequently used for the hydration of thin film lipid during the preparation of liposomes with the encapsulated drug. Two methods of the incorporation of imiquimod to liposomes were used. The first method represented insertion of the drug to lipids, the second was dissolution of the drug in the dendrimer solution. The concentration of encapsulated imiquimod, including the encapsulation efficacy, was...
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