20.500.12556/DKUM-69327 Večslojne medicinske matrice z modificiranim sproščanjem pentoksifilina za zdravljenje kronične venozne razjede Multilayer Polysaccharide Nanofilms for Controlled Delivery of Pentoxifyllin and Possible Treatment of Chronic Venous Ulcer Kronične rane predstavljajo velik socialno-ekonomski problem v zahodnem svetu. Eno najpomembnejših vrst kroničnih ran predstavlja kronična venozna razjeda, ki je odgovorna za okoli 80% vseh kroničnih razjed. Nova histo-patološka spoznanja so pokazala, de je lokalno, kronično vnetje v veliki meri odgovorno za patološke procese, ki vodijo do nastanka razjede kot tudi do upočasnjenega procesa celjenja. V tej študiji je predstavljen nov možen pristop k terapiji kronične venozne razjede, ki temelji na lokalnem dajanju potentne protivnetne zdravilne učinkovine, pentoksifilin (PTX). V ta namen so bile razvite ne-toksične polisaharidne večslojne medicinske obloge iz hitozana in alginata, ki zraven nadzorovanega sproščanja zdravilne učinkovine, že same pozitivno vplivajo na potek celjenja kroničnih ran. V okviru razvoja in optimizacije postopkov priprave omenjenih medicinskih oblog so bili pripravljeni in okarakterizirani najprej 2D modelni večslojni nosilni materiali, ter nato še obložena 3D alginatna koprena. S pomočjo različnih analiznih metod, smo dokazali uspešno pripravo večslojnih medicinskih oblog z dodanim PTX. Z analizo in vitro sproščanja je bilo pokazano, da tako pripravljene medicinske obloge omogočajo nadzorovano, dvo-stopenjsko sproščanje vodotopnega PTX. S pomočjo študij na humanih kožnih celicah smo pokazali biokompatibilnost večslojnih matric z dodatkom PTX. Za konec smo na osnovi eksperimenta na humanih monocitih potrdili tudi, da so pripravljene večslojne medicinske obloge preko delovanja PTX, uspešno zavrle sproščanje TNF-alfa, ki je ključen vnetni mediator pri kroničnih venoznih razjedah. Chronic wounds represent a huge socio-economical problem in the western sociality. One of the most common types of chronic wounds, is the chronic venous ulceration, which accounts for 80% of all chronic wounds. New histo-pathological insights have revealed that chronic local inflammation, which is believed to be preferentially caused by by chronic venous insufficiency, is one of the major causes for the development and poor healing of chronic wounds. In this study we represent a new approach for the treatment of chronic venous ulcers, which is based on the local application of a potent anti-inflammatory drug, pentoxifyllin (PTX). TO achieve controlled release of PTX, and hence provide an efficient and safe local treatment, a non-toxic, multi-layered polysaccharide matrix based on alginate and chitosan was developed. Besides the controlled drug release, such composition has a well-known positive effect on wound healing on its own. As part of their development, 2D model multilayer matrices, as well as functionalized 3D alginate fleece was prepared and characterized. With the help of different analytical methods, it was possible to demonstrate the successful preparation of multilayer matrices with the added PTX. By analysing the in vitro release, it has been shown that the prepared matrices allow a controlled release of the incorporated substance. Further analysis of the drug release profiles has shown, that a two-step release mechanism of the substance was achieved. The biocompatibility of multilayer matrixces with the added PTX was demonstrated through cellular studies on human skin derived fibroblasts. Additional cellular testing using human monocytes confirmed our hypothesis, that the controlled release of PTX is able to inhibit the secretion of TNF-alpha. Kronična venozna rana vnetje pentoksifilin hitozan alginat Chronic venous ulcer inflammation pentoxifyllin chitosan alginate true true false Slovenski jezik Angleški jezik Doktorsko delo/naloga 2018-01-03 20:02:57 2018-10-10 11:31:43 2022-08-01 17:19:27 2019-07-11 17:28:21 2018 0 Maribor 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 296867584 URN:SI:UM:DK:8XHU3EJ6 DOK_Stana_Jan_2018.pdf DOK_Stana_Jan_2018.pdf 1 DDCD519329EF05D7D91F1B984EB4F09F b20588d2c4857d919e119951c7ddadacfd7f88b4bba9c4661383d7fc69d75219 6b2a8d06-7c10-11eb-bb7a-00155d0001ca 20.500.12556/dkum/7687cb3e-f43f-4fd8-a1e4-64a491d44916 https://dk.um.si/Dokument.php?lang=slv&id=130481 Medicinska fakulteta 0 0 0