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Parodontalna bolezen je kronično vnetje dlesni in obzobnega tkiva, ki lahko privede do nastanka obzobnih žepov in izpada zob. Eden izmed načinov zdravljenja bolezni je uporaba protibakterijskih učinkovin v obliki tablet ali kapsul. Pomanjkljivost takšnega zdravljenja je lahko premajhna terapevtska koncentracija učinkovine v obzobnem žepu, ki vodi v razvoj bakterijske rezistence. Z uporabo lokalnega dostavnega sistema se tem pomanjkljivostim lahko izognemo, a moramo z vidika pacientu prijazne oblike zagotoviti podaljšano sproščanje učinkovine. V ta namen smo v magistrski nalogi izdelali enoslojna in dvoslojna nanovlakna iz hidrofobnega polimera polikaprolaktona (PCL) s hidrofilno učinkovino metronidazolom (MNZ) in proučevali procesne parametre, pri katerih bi dobili nanovlakna s sproščanjem učinkovine od 7 do 14 dni. Enoslojna nanovlakna smo izdelali z elektrostatskim sukanjem raztopin PCL, pri čemer smo spreminjali koncentracijo in molekulsko maso polimera, zmes organskih topil in količino vgrajene učinkovine. Ugotovili smo, da je za strukturo nanovlaken brez vozlov potrebno uporabiti 15 % raztopino PCL. Najtanjša in najbolj homogena nanovlakna, s 5 % MNZ, ki so sproščala učinkovino več kot 7 dni, smo dobili z raztopino s 15 % PCL v zmesi topil mravljične in ocetne kisline v razmerju 1 : 3. Ob povečanju MNZ na 10 % v ogrodju z enako sestavo se je vsa učinkovina sprostila že v 2 dneh. Kot prvi smo ugotovili, da večja debelina plasti nanovlaken upočasni hitrost sproščanja MNZ. Dvoslojna nanovlakna smo izdelali iz polimernih raztopin polivinil alkohola (PVA) za sredico in PCL za skorjo z elektrostatskim sukanjem skozi koaksialno šobo. Pri uporabi hidrofilnega polimera PVA v sredici se je sprostil ves MNZ v 8 urah, z uporabo hidrofobnega PCL, se je sproščanje podaljšalo na 2 dni. Z uporabo različnih organskih topil za PCL v sredici in skorji smo dosegli podaljšano sproščanje od 7 do 16 dni. Najboljše rezultate sproščanja smo dobili pri nanovlaknih s 3,6 % MNZ v 10 % PCL v zmesi topil diklorometana in dimetilformamida v razmerju 3 : 2 v sredici in v 15 % PCL v zmesi topil mravljične in ocetne kisline v razmerju 1 : 3 v skorji. Z uporabo ustrezne koncentracije PCL in zmesi topil smo izdelali enoslojna in dvoslojna nanovlakna, ki so podaljšano sproščala MNZ 7 do 14 dni in predstavljajo nov dostavni sistem. Protibakterijsko učinkovitost razvitih nanovlaken proučujejo in vitro na fibroblastih in parodontopatogenih bakterijah. Periodontal disease is a chronic inflammation of gums and periodontal tissue, which can lead to formation of periodontal pockets and teeth loss. One of the ways to treat the disease is with antimicrobial drugs in form of tablets or capsules. The disadvantage of such treatment is small concentration of active ingredient at periodontal pockets, which can lead to bacterial resistance. By using local drug delivery system, these deficiencies can be avoided. To achieve patient-friendly use, we want to obtain prolonged release of an active substance. For this purpose, we developed uniform and core-shell nanofibers from hydrophobic polymer – polycaprolactone (PCL) with an incorporated hydrophilic drug – metronidazole (MNZ), and studied essential process parameters to obtain nanofibers with sustained release of the active ingredient from 7 to 14 days. Uniform nanofibers were developed with electrospinning process of PCL solutions. Process of electrospinning was observed, while changing concentration and molecular weight of polymer, using different organic solvents and amount of MNZ. Nanofibers without beads were obtained when using 15 % PCL solution. The thinnest nanofibers with the most homogenous structure were obtained using 5 % MNZ and 15 % PCL dissolved in acetic and formic acid 1 : 3. These nanofibers prolonged the release over 7 days. When the drug loading of nanofibers was increased to 10 %, all the active ingredient was released in 2 days. We were first to discover that the thicker nanofiber mat resulted in a prolonged release up to 14 days. Core-shell nanofibers were made from polyvinylalcohol (PVA) solution as a core and PCL as a shell solution, and electrospun with coaxial nozzle. With hydrophilic polymer PVA in core, MNZ was released in 8 hours, whereas hydrophobic PCL in core, we achieved prolonged release for 2 days. With the use of different organic solvents for PCL in the core and shell, we obtained prolonged release from 7 to 16 days. Best results were achieved with nanofibers loaded with 3,6 % MNZ in 10 % PCL solution of dichlorometane and dimethylformamide 3 : 2 as the core, and 15 % PCL solution of formic and acetic acid 1 : 3 as the shell. With the use of appropriate PCL concentration and mixture of solvents, uniform and core-shell nanofibers were obtained, which prolonged the release of MNZ from 7 to 14 days. They represent a new drug delivery system. The antibacterial efficacy of the developed nanofibers is investigated in in vitro studies on fibroblasts and periodontopathogenic bacteria. |
