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.
|
