Načrtovanje in priprava skupkov magnetnih nanodelcev z mezoporozno oblogo iz silicijevega dioksida

Rupar, Katarina (avtor), Kocbek, Petra (mentor), Kralj, Slavko (komentor)

Omejitev klasičnih farmacevtskih oblik predstavlja nespecifično porazdeljevanje in neciljano nalaganje zdravilnih učinkovin v organizmu, kar je gonilo razvoja novih dostavnih sistemov za ciljano dostavo zdravilnih učinkovin. Zlasti aktualni so dostavni sistemi, ki se odzivajo na dražljaje iz okolja. Takšni dostavni sistemi so lahko magnetno vodljivi, zato omogočajo ciljano dostavo zdravilnih učinkovin s pomočjo gradienta magnetnega polja. V tej skupini so posebej zanimivi superparamagnetni nanodelci železovega oksida, ki so s strani regulatornih agencij odobreni kot varni za ljudi. Priprava koloidno stabilne suspenzije takšnih delcev je relativno enostavna, saj se takšni delci v odsotnosti zunanjega magnetnega polja obnašajo kot nemagnetni in se posledično magnetno ne agregirajo. V okviru raziskav magistrskega dela smo načrtovali in pripravili magnetno vodljive nanoskupke. Pripravili smo magnetno vodljive nanoskupke in jih obložili s tanko neporozno oblogo iz silicijevega dioksida (silike) z uporabo dveh različnih postopkov. Tanka obloga iz silike zaščiti magnetne nanodelce ter zagotovi primerno koloidno stabilnost disperzije. Prvi postopek oblaganja je bil neustrezen zaradi težav s koloidno stabilnostjo delcev med sintezo, kar je povzročilo združevanje nanoskupkov. Drugi postopek je bil zaradi dodatka površinsko aktivne snovi uspešen, zato smo tako pripravljene nanoskupke uporabili za nadaljnje raziskave. Na tanko oblogo silike smo dodali debelejšo oblogo iz mezoporozne silike, ki omogoča vgrajevanje zdravilnih učinkovin v nanodostavni sistem. Osredotočili smo se na pripravo obloge z relativno velikimi in radialno usmerjenimi porami. Oblogo iz mezoporozne silike smo pripravili po treh različnih postopkih. Pri tem smo proučevali uporabo dveh različnih baz, in sicer trietanolamina in tris(hidroksimetil)aminometana. Pri odstranjevanju površinsko aktivnih snovi po sintezi mezoporozne obloge smo ugotovili, da je nastala najbolj robustna obloga v primeru, ko smo uporabili bazo tris(hidroksimetil)aminometan. Takšna obloga je bila odporna na ostre pogoje med spiranjem, kot sta povišana temperatura in uporaba ultrazvoka. V nadaljnjih raziskavah smo na površino magnetnih nanoskupkov uspešno uvedli amino in karboksi funkcionalne skupine, kar smo ovrednotili z meritvami zeta potenciala delcev. Za pripravo koloidno stabilnih nanoskupkov, ki bodo v prihodnje omogočali vgradnjo zdravilnih učinkovin, smo uporabili še dva postopka pegiliranja, pri čemer smo z neposredno vezavo PEG-silana na površino magnetnih nanoskupkov z oblogo iz mezoporozne silike pripravili obetaven sistem za nadaljnji razvoj magnetno vodljivega nanodostavnega sistema za ciljano dostavo zdravilnih učinkovin.

• Jezik: Slovenski jezik
• Ključne besede: magnetni nanoskupki, superparamagnetni nanodelci železovega oksida, mezoporozna obloga iz silike, nanodostavni sistemi
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2021
• PID: 20.500.12556/RUL-130468
• Datum objave v RUL: 15.09.2021

RUPAR, Katarina, 2021, Načrtovanje in priprava skupkov magnetnih nanodelcev z mezoporozno oblogo iz silicijevega dioksida [na spletu]. Magistrsko delo. [Dostopano 8 marec 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=130468

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Design and preparation of magnetic nanoparticle clusters with mesoporous silica shell

Izvleček

The limitation of classical pharmaceutical dosage forms is represented by the non-specific distribution and non-targeted delivery of active ingredients in the body, which is the driving force for the development of novel targeted drug delivery systems. Delivery systems that respond to environmental stimuli are particularly relevant. Such delivery systems can be magnetically guidable, thus enabling targeted drug delivery using a magnetic field gradient. Of particular interest in this group are superparamagnetic iron oxide nanoparticles, which are approved by regulatory agencies as safe for humans. The preparation of a colloidally stable suspension of such particles is relatively simple, since they behave as non-magnetic in the absence of an external magnetic field and consequently do not aggregate magnetically. In the scope of the master's thesis, magnetically-responsive nanoclusters were designed and prepared. Magnetic nanoclusters were prepared and coated with a thin non-porous layer of silicon dioxide (silica) using two different procedures. A thin silica coating protects the magnetic nanoparticles and provides adequate colloidal dispersion stability. The first procedure was unfavorable due to problems with colloidal stability during synthesis, which resulted in the aggregation of nanoclusters. The second procedure was successful due to the addition of surfactant, thus the nanoclusters coated by this procedure were used for further research. They were coated by an additional thicker layer of mesoporous silica, which was added to the thin silica coating. Mesoporous silica layer enables the loading of the active ingredients. We focused on the preparation of relatively large and radially oriented pores. The mesoporous layer of silica was prepared by three different procedures. The application of two different bases was investigated, namely triethanolamine and tris (hydroxymethyl) aminomethane. When removing surfactants after the synthesis of mesoporous coating, we discovered that the most robust coating was formed when the tris (hydroxymethyl) aminomethane was used as the base. Such a coating was resistant to harsh conditions during rinsing, such as elevated temperature and the use of ultrasound. In further research, we successfully introduced amino and carboxy groups on the surface of nanoclusters, which was evaluated by measuring zeta potential of the particles. To prepare colloidally stable nanoclusters for future drug loading, we used two pegylation procedures, whereby direct binding of PEG-silane to the surface of nanoclusters with mesoporous silica resulted in a promising system for further development of magnetically guidable nanodelivery system for targeted drug delivery.

• Ključne besede: magnetic nanoclusters, superparamagnetic iron oxide nanoparticles, mesoporous silica coating, nanodelivery systems