Vpliv procesnih parametrov elektrostatskega sukanja na debelino, homogenost, sproščanje in bioadhezivnost polikaprolaktonskih nanovlaken z metronidazolom

Vrčon, Maruša (avtor), Kristl, Julijana (mentor), Zupančič, Špela (komentor)

Parodontalna bolezen je zelo razširjena kronična vnetna bolezen dlesni, kjer trenutno osnovno zdravljenje ne zagotavlja trajno pozitivnih rezultatov pri vseh pacientih. Posledično so v razvoju nanozdravila s ciljano dostavo učinkovin v obzobne žepe, nadzorovanim sproščanjem ter podaljšanim zadrževanjem na mestu aplikacije za doseganje boljšega učinka. Namen magistrske naloge je bil izdelati polikaprolaktonska nanovlakna z metronidazolom s terapevtskim odmerkom, jih ovrednotiti in primerjati z izdelanim filmom z enako sestavo kot je sestava nanovlaken. V magistrski nalogi smo izdelali nanovlakna z nekajurnim elektrostatskim sukanjem in preučevali vpliv različnih parametrov zbiranja formulacije na homogenost dobljenega vzorca z merjenjem debeline plasti nanovlaken in testi po Ph. Eur. 10.0 (Enakomernost mase, vsebnosti enoodmernih enot in enakomernost odmernih enot). Filme smo izdelali z vlivanjem polimerne raztopine in izhlapevanjem topil, obema dostavnima sistemoma pa smo z vrstično elektronsko mikroskopijo ovrednotili morfologijo. Preučevali smo tudi zaostanek rezidualnih topil v nanovlaknih, sproščanje metronidazola z validirano metodo UPLC in bioadhezivnost pripravljenih formulacij. Dokazali smo, da se s časom zbiranja nanovlaken veča debelina izdelane plasti, hkrati pa se veča tudi masa posameznih enot. Najbolj homogeno plast nanovlaken smo dobili z zbiranjem vzorca na rotirajoči valj, saj je le-ta ustrezal testu enakomernosti mase. Vgradnja metronidazola je bila uspešna s povprečno vsebnostjo 100,0 %. Celotni plasti nanovlaken, tako z valja kot plošče, sta ustrezali testoma enakomernosti vsebnosti in odmernih enot, saj je bila vsebnost vseh testiranih enot med 85 in 115 %, sprejemljiva vrednost (AV) pa manjša od 15,0. Ugotovili smo, da je sušenje nanovlaken pomemben korak pri izdelavi, saj smo z njim zmanjšali delež zaostanka topil v vzorcu pod mejo detekcije, kar je vplivalo na počasnejše sproščanje metronidazola iz nanovlaken. Počasnejše sproščanje smo dobili tudi pri nižji temperaturi medija ter iz debelejše plasti nanovlaken. V primerjavi z nanovlakni pa se je metronidazol hitreje sproščal iz filma. V samih bioadhezivnih lastnostih med formulacijama ni bilo signifikantne razlike, so pa nanovlakna izkazovala večjo odpornost proti mehanski obremenitvi. V magistrski nalogi smo tako dokazali, da lahko z optimizacijo procesnih parametrov elektrostatskega sukanja izdelamo homogena, bioadhezivna, mehansko odporna nanovlakna s podaljšanim sproščanjem učinkovine.

• Jezik: Slovenski jezik
• Ključne besede: Nanovlakna, elektrostatsko sukanje, parodontalna bolezen, metronidazol, polikaprolakton, homogenost, debelina, bioadhezivnost.
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2020
• PID: 20.500.12556/RUL-117495
• Datum objave v RUL: 14.07.2020

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: The effect of electrospinning process parameters on thickness, homogeneity, release and bioadhesivity of polycaprolactone nanofibres with metronidazole

Izvleček

Periodontal disease is a widespread chronic inflammatory gum disease for which the currently existing treatment does not guarantee permanent positive results in case of all patients. Consequently, nanomedicines are in development to achieve more effective treatment. The goal of this Master’s thesis was to design polycaprolactone nanofibers with metronidazole with a therapeutic dose, to evaluate and compare them with a film that was made with the same composition as the nanofibers. We electrospun nanofibers and studied the effects of different collection parameters on the homogeneity of the obtained sample by measuring the nanofiber layer thickness and conducting tests in accordance with Ph. Eur. 10.0 (Uniformity of mass of single-dose preparations, Uniformity of content of single-dose preparations, Uniformity of dosage units). The films were made by solution casting method and the morphology of both delivery systems was evaluated by scanning electron microscopy. We also studied the residual solvents in nanofibers, the metronidazole release by a validated UPLC method and the bioadhesivity of the prepared formulations. Results have shown that with longer time of electrospinning we could prepare thicker and heavier nanofiber mat. The most homogeneous nanofiber layer was obtained by collecting a sample on a rotating cylinder, since only in this case the mass uniformity test was conformed. The metronidazole incorporation into nanofibers was successful with an average content of 100.0%. The formulations collected on the cylinder and on the plate corresponded to the uniformity of content and uniformity of dosage units tests, since the content level for all tested units ranged from 85 to 115%, and the AV value was lower than 15.0. The drying of nanofibers is an important step in production, since it enabled the reduction of the residual solvents in the sample below the detection limit. Such nanofibers also resulted in a slower release of metronidazole as before drying. A slower release was also attained at a lower temperature of the medium and from a thicker nanofiber layer. Meanwhile, the release of the metronidazole from the film was faster when compared to the nanofibers. There were no significant differences in the bioadhesive properties of the two formulations, although the nanofibers demonstrated a higher level of resistance towards mechanical stress. Therefore, this Master’s thesis proves that by optimising the processing parameters of electrospinning, we can produce homogeneous, bioadhesive, mechanically resistant nanofibers with prolonged drug delivery.

• Ključne besede: Nanofibers, electrospinning, periodontal disease, metronidazole, polycaprolactone, homogeneity, thickness, bioadhesivity.