• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 1
  • Tagged with
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • 1
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Sinteza, karakterizacija i biološka ispitivanja fulerenol/doksorubicin nanokompozita / Synthesis, characterisation and biological activity investigation of fullerenol/doxorubicin nanocomposite

Jović Danica 19 April 2018 (has links)
<p>U radu je predstavljena sinteza i karakterizacija&nbsp; novog fulerenol/doksorubicin nanokompozita, sintetisanog sa ciljem dobijanja potencijalne nove nanoformulacije postojećeg antineoplastika doksorubicina, koja bi pokazala veću biolo&scaron;ku aktivnost uz smanjenje neželjenih sporednih efekata koje sam lek izaziva, na prvom mestu kardiotoksičnosti.</p><p>Nanokompozit fulerenol/doksorbicin je okarakterisan brojnim&nbsp; metodama prateći dva osnovna eksperimentalna pristupa: molekulsko-spektroskopske metode (XPS, denzitometrija i transportne osobine, NMR, UPLC, Ramanska i UV-spektroskopija, SFM) i metode&nbsp; nanokarakterizacije (DLS, AFM, TEM), kao i računske simulacije(RDF). Osnovni cilj ispitivanja je bila detekcija postojanja&nbsp;nekovalentnog nanokompozita koji ostvaruju doksorubicin i fulerenolske nanočestice u vodenom rastvoru. Rezultati karakterizacije jasno i nedvosmisleno ukazuju na postojanje nekovalentnih interakcija unutar nanokompozita, &scaron;to dalje utiče na organizaciju i udruživanje čestica, a &scaron;to uslovljava i drugačiju biolo&scaron;ku aktivnost takvog sistema u odnosu na pojedinačne komponente.&nbsp; Rezultati biolo&scaron;kih ispitivanja na&nbsp;<em>in vitro</em>&nbsp;modelu različitih tumorskih ćelijskih linija pokazuju&nbsp; značajan&nbsp;antiproliferativni efekat nanokompozita, kao i selektivnost prema tumorskim u odnosu na zdravu ćelijsku liniju. Eksperimenti na <em>in vivo</em> modelu zebrica potvrđuju smanjenje toksičnosti nanokompozita u poređenju sa lekom, primarno kardiotoksičnosti. Računske simulacije, mikroskopski i spektroskopski podaci, kao i rezultati&nbsp; <em>in vitro</em> i <em>in vivo</em> studija ukazuju na to da nekovalentne interakcije između fulerenola i doksorubicina mogu biti ključni korak u stvaranju sinergističkog sistema za dostavu leka u biolo&scaron;ki sistem.</p><p>Multipotentnost fulerenola kao nanonosača lekova i nespecifičnost strukture doksorubicina kao leka, ukazuje na to da bi fulerenol mogao biti efikasan nanonosač i drugih antineoplastika, &scaron;to daje prostora za unapređenje antitumorskih osobina lekova posredstvom istovremene administracije leka.</p> / <p>The focus of this thesis was the synthesis and characterization of a novel fullerenol/doxorubicin nanocomposite, with the aim to obtain a potential nanoformulation of antineoplastic drug doxorubicin, which would&nbsp; express greater biological activity and lower level of adverse effects than the drug itself, in the first place cardiotoxicity.</p><p>Nanocomposite fullerenol/doxorubicin was characterized by means of numerous methods&nbsp; following two main experimental approaches: molecular-spectroscopic methods (XPS, densitometry and transport properties, NMR, UPLC, Raman and UVspectroscopy, SFM) and mehods of&nbsp; anocharacterisation&nbsp; (DLS, AFM,&nbsp; TEM), as well as computer simulations (RDF). The goal of characterization was detection of&nbsp; non-covalent interactions within nanocomposite that are established between fullerenol nanoparticles and doxorubicin in aqueous solution. The results clearly indicate the existence of non- covalent interactions within nanocomposite that affect the organization and assembling of the particles, which further exhibit different biological activity of such a system in comparison to components themselves. Results of biological activity on <em>in vitro </em>model of different tumor cell lines show significant antiproliferative effect of&nbsp; nanocomposite, as well as selectivity towards tumor cell lines. Experiments conducted on <em>in vivo</em> zebrafish model confirm the lowering ofthe adverse effects of the drug, especially cardiotoxicity, in case when nanocomposite was applied. Computer simulations, microscopic and&nbsp; spectroscopic results combined with encouraging <em>in vitro </em>and <em>in vivo</em> results point out&nbsp; that non-covalent interactions between fullerenol nanoparticles and doxorubicin may present the keyrole in formation of a synergistic system for nanodrug delivery into biological system. Multipotential of fullerenol nanoparticles as a nanocarrier and non-specific structure of doxorubicin as a drug imply that fullerenol may serve as a efficient nanocarrier of numerous other antineoplastics, which further allows the improvement of antitumor properties of drugs withsimultaneous drug administration.</p>

Page generated in 0.0281 seconds