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Title:Development of polymeric materials with rutin and polyrutin for healing of chronic leg ulcers
Authors:ID Pivec, Tanja (Author)
ID Stana Kleinschek, Karin (Mentor) More about this mentor... New window
ID Maver, Uroš (Comentor)
Files:.pdf DOK_Pivec_Tanja_2018.pdf (7,34 MB)
MD5: 1E0CE4CF21B5204C216F6C59C89765C6
PID: 20.500.12556/dkum/cda8db9d-30c9-4be8-b1ed-f8b6d2b419b0
 
Language:English
Work type:Doctoral dissertation
Typology:2.08 - Doctoral Dissertation
Organization:FS - Faculty of Mechanical Engineering
Abstract:In this work, the development of cellulose wound dressing materials with rutin (RU) and polyrutin (PR) for the healing of chronic leg ulcers is presented as a new approach of local treatment of this wound type. The flavonoid rutin is a known antioxidant substance of plant origin with wound healing promoting properties. Despite the proven beneficial properties of rutin, its potential application in wound healing is limited due to its low water solubility. This limitation can be overcome by polymerization of rutin into polyrutin. In this work an enzymatic polymerization of rutin in water without addition of organic solvents was performed to obtain a water-soluble polymer polyrutin. The chemical structure of rutin and polyrutin were investigated using UV-Vis spectroscopy, nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, size-exclusion chromatography and potentiometric titrations. Biological activity related to a desired positive influence on chronic leg ulcers was investigated through the determination of the antioxidant activity, iron-chelation ability, cell viability, determination of cell proliferation and through use of the so called “scratch assay” to measure in vitro wound healing performance. Results indicate that rutin and polyrutin have a positive influence on the healing of chronic wounds. Rutin and polyrutin water dispersions at different pH and ionic strength were further characterised by means of dynamic light scattering in order to determine the size of particles and their pH dependent ζ-potential. The knowledge gained from these measurements aided the systematic interaction studies of rutin and polyrutin dispersions with cellulose-based surfaces via model and real wound healing systems. The model cellulose surfaces were thin films prepared by dissolution of trimethylsilyl cellulose in tetrahydrofuran, spin-coating of this solution on sensors of a quartz crystal microbalance (QCM-D) and subsequent regeneration of trimethylsilyl cellulose to cellulose with acid vapors. The influence of pH, salt concentration, and rutin/polyrutin concentration on the interaction with cellulose thin films was evaluated by means of a quartz crystal microbalance with dissipation. This knowledge was transferred to the application of the coatings on real wound healing systems i.e. cellulose non-wovens. The surface morphology was further characterised on model and real wound healing systems. The antioxidant activity and release kinetics were investigated for a real wound healing system, similar to the clinically used, cellulose based wound dressing materials. The main results showed that a higher solubility of polyrutin at low ionic strength contributes to the formation of continuous layers of polyrutin on cellulose surface, while the low solubility of rutin and reduced solubility of polyrutin at higher ionic strengths contribute to deposition of particles of rutin and polyrutin on the cellulose surface. The presence of particles on the surface of non-woven cellulose fibres led to a faster initial release of rutin and polyrutin. On the contrary, a continuous layer of the well soluble polyrutin contributes to a prolonged release. Namely, adsorption of the water soluble polyrutin at pH 2 without the addition of salt results in higher masses of attached polyrutin that release slower and over longer time periods. Since wound dressing materials for chronic leg ulcers often require a lower frequency of dressing change, the latter could provide an efficient therapeutic approach to their treatment.
Keywords:Chronic wounds, Wound dressings, Cellulose, Polymerization of flavonoids, Rutin, Polyrutin
Place of publishing:Maribor
Publisher:[T. Pivec]
Year of publishing:2018
PID:20.500.12556/DKUM-69375 New window
UDC:[678.542.3.017.86+577.164.3]:61(043.3)
COBISS.SI-ID:21506326 New window
NUK URN:URN:SI:UM:DK:YIMDGQOM
Publication date in DKUM:11.06.2018
Views:2024
Downloads:282
Metadata:XML DC-XML DC-RDF
Categories:KTFMB - FS
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Licences

License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.
Licensing start date:15.01.2018

Secondary language

Language:Slovenian
Title:Razvoj polimernih materialov z rutinom in polirutinomom za zdravljenje golenjih razjed
Abstract:V doktorski nalogi je predstavljen razvoj celulozne medicinske obloge z rutinom in polirutinom namenjene oskrbi kronične golenje razjede, ki predstavlja nov pristop k izboljšanju lokalnega načina zdravljenja teh vrst ran. Za flavonoid rutin je dokazano, da deluje antioksidativno in protivnetno ter pripomore k hitrejšemu celjenju ran. Kljub njegovim pozitivnim učinkom pa je njegova potencialna uporaba za zdravljenje ran omejena zaradi njegove slabe vodotopnosti. To omejitev lahko odpravimo s polimerizacijo rutina v polirutin. V doktorski disertaciji je predstavljena encimska polimerizacija rutina v vodi, brez dodajanja organskih topil, z namenom doseganja njegove vodotopnosti in s tem njegove lažje vezave na nosilni celulozni material. Kemijska struktura rutina in polirutina je ovrednotena z ultravijolično in vidno spektroskopijo (UV-Vis), z jedrsko magnetno resonanco (NMR), z infrardečo spektroskopijo, z velikostno izključitveno kromatografijo in s pH potenciometrično titracijo. Za zdravljenje kroničnih ran pomembne bioaktivne lastnosti so bile ovrednotene z določanjem antioksidativne aktivnosti, sposobnosti vezave Fe2+ ionov, ovrednotenjem celične viabilnosti in proliferacije, ter vpliva na hitrost zapiranja rane in vitro. Iz tega dela doktorske disertacije lahko povzamemo, da rutin in vodotopen polirutin pozitivno vplivata na zdravljenje kroničnih ran. V nadaljevanju je na sistematičen način preučena velikost delcev in ζ-potencial disperzij rutina in polirutina pri različnih koncentracijah soli ter pri različnih vrednostih pH, kar je pomembno za interpretacijo interakcij rutina in polirutina s celulozno površino. Slednje je bilo preučeno na modelni in na realni medicinski oblogi. Modelno celulozno površino so predstavljali tanki celulozni filmi pripravljeni z napravo za nanašanje ultra-tankih plasti z metodo vrtenja, in sicer na kvarčne kristale, ki so hkrati substrat in senzor za uporabo kvarčne mikrotehtnice (QCM-D). Slednjo smo uporabili za spremljanje interakcij med rutinom/polirutinom in celulozno površino pri različnih pH, različnih ionskih močeh in različnih koncentracijah rutina/polirutina. Znanje pridobljeno v tem delu doktorske disertacije je bilo preneseno na funkcionalizacijo celulozne netkane koprene, ki predstavlja realno medicinsko oblogo. Morfološke lastnosti adsorbiranih plasti polirutina so bile dodatno okarakterizirane z mikroskopom na atomsko silo in vrstičnim elektronskim mikroskopom na modelni in realni medicinski oblogi, medtem ko je bila antioksidativna aktivnost in kinetika sproščanja preučena na realni medicinski oblogi. Glavni rezultati kažejo, da višja topnost polirutina pri nizki ionski moči prispeva k njegovi višji adsorpciji na celulozno površino v obliki enakomerne kontinuirane plasti, nasprotno pa tvorba aglomeratov pri višji ionski moči prispeva k odlaganju rutina in polirutina v obliki delcev na vlakna v netkani kopreni. Čeprav skoraj vsi z rutinom in polirutinom obdelani vzorci netkane koprene izkazujejo antioksidativno aktivnost, ima oblika rutina in polirutina (kontinuirana plast ali delci) vpliv na profil sproščanja. Ugotovili smo, da prisotnost delcev rutina na vlaknih prispeva k hitri sprostitvi rutina v začetnem času, medtem ko kontinuirane plasti adsorbiranega polirutina prispevajo k dolgotrajnemu sproščanju. Natančneje, adsorpcija vodotopnega polirutina pri pH 2 brez dodatka soli vodi do višje mase adsorbiranega polirutina, ki se sprošča počasneje skozi daljše časovno obdobje. Z vidika uporabe materiala za oskrbo kroničnih golenjih razjed, ki zahteva manj pogosto menjavo obloge, je to obetaven pristop k razvoju celulozne medicinske obloge z antioksidativnim delovanjem za zdravljenje kronične golenje razjede.
Keywords:Kronične rane, Medicinske obloge za rane, Celuloza, Polimerizacija flavonoidov, Rutin, Polirutin


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