Dendrimers are characterized as synthetic, spherical macromolecules with tree- like branched structures. Their well-controlled sizes (3 - 10 nm), ease of functionalization, high water solubility, well-defined chemical structure, and biocompatibility make these nanomaterials attractive for a wide spectrum of promising biomedical applications. Peptide dendrimers and polyamidoamine (PAMAM) dendrimers have been used to date as effective transdermal or topical drug delivery systems, with the latest in a much greater extent. The structural characteristics of the aforementioned molecules guided us to design a novel repeating unit for dendrimers (monomer) possessing amino branching point and able to afford generation expanding through repeating amide bonds. The novel monomer, after appropriate modifications, was used to develop lower generations of polyamidoamino dendritic structures having amide groups and amino-branching points in their interior. The new dendrimers were isolated and fully characterized by typical spectroscopic technics. The final molecules will be used in human skin permeation experiments and will be evaluated for their effect on skin permeability.

Effect of the concentration of amino-decorated polyamidoamine dendrimers with ethylenediamine core at the (trans)dermal delivery of 5-Fluorouracil Pavlína Chladová Dendrimers are synthetic, symmetrically tree-like branched molecules. They are composed of repeating units (monomers). They have high density of surface functional groups and spherical shape in solution. Since their molecular weight is highly controllable, they are characterized by monodispersity and this is their main difference from classical polymers. Dendrimers have a wide spectrum of applications in biomedicine. Due to the empty space between the branches of the molecule, they can encapsulate drugs, and by conjugation and complexation to the surface groups, they are able to carry even larger drug molecules. Thus, dendrimers can be used as drug delivery systems. In addition, they have been used for skin application of several active molecules, either as topical or transdermal delivery. Suitable properties for (trans)dermal application have been demonstrated for dendrimers which consist of monomers with amine groups and are connected with amide bonds. The goal of this thesis was the preparation of dendrimers with these characteristics and the evaluation of their concentration influence to the permeability of 5-Fluorouracil (5-FU) to human...

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...