Razvoj in vrednotenje polimernih nanovlaken s simvastatinom

Filipič, Neja (avtor), Kocbek, Petra (mentor), Zupančič, Špela (komentor)

Parodontalna bolezen je razširjena kronična vnetna bolezen, ki je zelo zahtevna za zdravljenje. Trenutno razpoložljivi terapevtski pristopi običajno vodijo le v kratkotrajno ozdravitev. V magistrski nalogi smo razvijali nanovlakna s simvastatinom za imunomodulatorno zdravljenje parodontalne bolezni. Vlakna smo izdelali iz Kollidona SR, polietilenoksida, polivinilpirolidona, polikaprolaktona in Soluplusa. Vanje smo vgrajevali slabo vodotopno ter kemijsko nestabilno učinkovino, simvastatin, ter proučevali morfologijo nanovlaken in sproščanje učinkovine iz vlaken. Profili sproščanja učinkovine iz polimernih nanovlaken kažejo hitro sproščanje simvastatina, kar nakazuje, da je simvastatin med izdelavo nanovlaken na osnovi Soluplusa, polivinilpirolidona, polietilenoksida in polikaprolaktona vsaj delno prešel v amorfno obliko. V sink pogojih je prišlo pri formulacijah s hidrofilnimi polimeri do zelo hitre sprostitve učinkovine. Kljub hidrofobnosti se je učinkovina prej kot v 2 h sprostila tudi iz nanovlaken na osnovi polikaprolaktona. Iz nanovlaken na osnovi Kollidona SR se učinkovina v 24 h ni popolnoma sprostila. Z izdelavo nanovlaken na osnovi polivinilpirolidona smo uspeli povečati topnost simvastatina v non sink pogojih. Z raztapljanjem nanovlaken smo dosegli stanje prenasičenja simvastatina, s tem pa koncentracijo učinkovine, ki ustreza terapevtski koncentraciji za zdravljenje parodontalne bolezni. Nanovlakna bi lahko lokalno namestili v obzobne žepke, ki nastanejo pri parodontalni bolezni. Realne koncentracije učinkovine na mestu delovanja in vivo je na osnovi preskusa sproščanja in vitro težko predvideti, saj je bil tudi pri preskusu v non sink pogojih volumen medija veliko večji, kot v obzobnem žepku pri parodontalni bolezni. Z diferenčno dinamično kalorimetrijo smo ugotovili, da je simvastatin v nanovlaknih na osnovi polivinilpirolidona vsaj deloma v amorfni obliki, kar je ugodno za povečanje topnosti učinkovine. Metoda, ki smo jo uporabili za določanje kristalnega stanja, pa se je izkazala kot neustrezna, saj je bilo tališče polimerov nižje od tališča simvastatina, zato se je le-ta lahko med analizo raztapljal v talini polimerov. Čeprav smo dostavni sistem oblikovali za namen lokalnega zdravljenja parodontalne bolezni, pa izboljšanje topnosti ter hitrosti raztapljanja simvastatina ter hitro sproščanje iz dostavnega sistema lahko vodijo tudi do boljše absorpcije simvastatina v črevesju pri peroralni uporabi, s čimer se lahko poveča njegova biološka uporabnost.

• Jezik: Slovenski jezik
• Ključne besede: elektrostatsko sukanje, nanovlakna, parodontalna bolezen, polimeri, prenasičenje, simvastatin, topnost
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2022
• PID: 20.500.12556/RUL-137332
• Datum objave v RUL: 11.06.2022

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Development and characterisation of simvastatin-loaded polymer nanofibers

Izvleček

Periodontal disease is a widespread chronic inflammatory disease, very difficult to treat. Currently available therapeutic approaches usually lead only to short-term recovery. In this master's thesis, we developed nanofibers with simvastatin for the immunomodulatory treatment of periodontal disease. The fibers were prepared from Kollidon SR, polyethylene oxide, polyvinylpyrrolidone, polycaprolactone and Soluplus. We incorporated a poorly water-soluble and chemically unstable drug, simvastatin, into the polymer nanofibers, and investigated the morphology of the nanofibers and the release of simvastatin from the fibers. Simvastatin release profiles show fast simvastatin release from Soluplus, polyvinylpyrrolidone, polyethylene oxide and polycaprolactone nanofibers, indicating simvastatin was at least partially converted to its amorphous form during the electrospinning process. Under sink conditions, simvastatin was released rapidly from formulations with hydrophilic polymers. Despite its hydrophobicity, simvastatin was also released from polycaprolactone nanofibers in less than 2 h. Simvastatin was not completely released from the Kollidon SR nanofibers within 24 h. We increased the solubility of simvastatin in non sink conditions by its incorporation in polyvinylpyrrolidone nanofibers. Dissolution of simvastatin from nanofibers resulted in supersaturated state and thus a concentration of dissolved simvastatin which corresponds to its therapeutic concentration for the treatment of periodontal disease was achieved. Nanofibers could be placed locally in the periodontal pockets that are formed in periodontal disease. It is difficult to predict the true concentrations of the drug at the affected site in vivo, since the volume of the medium in the experiment in vitro was much higher than in periodontal pockets. DSC analysis revealed that simvastatin in polyvinylpyrrolidone nanofibers was at least partially in amorphous form, which is favorable for increasing its solubility. However, the method for investigation of sample crystallinity was shown to be inadequate, since polymers melted at lower temperature than the drug, which could thus dissolve in polymer melt during the analysis. Although the delivery system was designed for the local treatment of periodontal disease, improving the solubility and dissolution rate of simvastatin and its rapid release from the delivery system could result in improved intestinal absorption after oral administration, which may increase its bioavailability.

• Ključne besede: electrospinning, nanofibers, periodontal disease, polymers, simvastatin, solubility, supersaturation