Razvoj nanovlaken z magnetnimi nanodelci za uporabo v biomedicini

Dragar, Črt (author), Kocbek, Petra (mentor), Kralj, Slavko (co-mentor)

Nanodelci in nanovlakna izkazujejo velik potencial za uporabo na številnih področjih v biomedicini, kot so dostava zdravilnih učinkovin, regeneracija tkiv, oskrba ran, diagnostika in teranostika. Med različnimi vrstami nanodelcev so v zadnjem času veliko pozornosti pritegnili magnetni nanodelci (MND), osnovani na železovem oksidu, najpogosteje maghemitu (?-Fe2O3) ali magnetitu (Fe3O4), ki imajo pri velikostih < ~ 20 nm superparamagnetne lastnosti. V doktorski disertaciji smo naslovili ključne izzive pri razvoju takšnih MND, in sicer zagotavljanje stabilnosti disperzij MND, vgrajevanje zdravilnih učinkovin v oblogo MND in varnost MND. Z namenom izboljšanja fizikalne stabilnosti MND smo kot inovativen pristop za pretvorbo disperzij MND v suho obliko uporabili metodo elektrostatskega sukanja, s katero smo MND vgradili v hidrofilna nanovlakna. Uspeli smo izdelati suh nesipek produkt z do 65 % (m/m) MND, ki je omogočal njihovo hitro, enostavno in učinkovito redispergiranje. Nadalje smo v hidrofilna nanovlakna uspešno vgradili štiri različne zdravilne učinkovine in dokazali, da lahko njihove fizikalno-kemijske lastnosti pomembno vplivajo na lastnosti nanovlaken. Razvili smo postopek vgradnje zdravilne učinkovine v MND z oblogo iz poroznega silicijevega dioksida in pripravljeno formulacijo MND z elektrostatskim sukanjem takoj pretvorili v suho obliko, s čimer smo želeli preprečiti agregiranje MND in neželeno sproščanje zdravilne učinkovine iz MND v disperzijo med shranjevanjem. Tako smo uspeli izdelati homogena nanovlakna s ~ 20,0 % (m/m) MND in ~ 4,2 % (m/m) zdravilne učinkovine. Kot prvi smo sistematično ovrednotili vpliv morfologije površine s silicijevim dioksidom obloženih MND na biološki odziv celic in vitro ter dokazali, da so MND z manjšimi porami na površini bolj varni kot tisti z večjimi. Z razvitimi inovativnimi pristopi smo odprli nove možnosti raziskav in naslovili nekatere ključne tehnološke izzive v razvoju nanodelcev. Z našimi odkritji smo tako prispevali svoj delček v mozaik spoznanj, ki so potrebna za zagotavljanje varnosti, učinkovitosti in kakovosti MND za uporabo v biomedicini.

• Language: Slovenian
• Keywords: Biološko vrednotenje, elektrostatsko sukanje, ibuprofen, magnetni nanodelci, nanodelci železovega oksida, nanovlakna, obloga iz mezoporoznega silicijevega dioksida, polietilenoksid, poloksamer 188, sušenje, teranostiki, vgradnja učinkovine.
• Work type: Doctoral dissertation
• Organization: FFA - Faculty of Pharmacy
• Year: 2023
• PID: 20.500.12556/RUL-152448
• Publication date in RUL: 25.11.2023

Secondary language

• Language: English
• Title: Development of nanofibers with magnetic nanoparticles for biomedical applications

Abstract

Nanoparticles and nanofibers have shown significant potential for their use in biomedicine, including drug delivery, tissue regeneration, wound care, diagnostics, and theranostics. Among different types of nanoparticles, magnetic nanoparticles (MNPs), based on iron oxide, most commonly magnetite (Fe3O4) or maghemite (γ-Fe2O3), have recently attracted attention as they show superparamagnetic properties at sizes < ~20 nm. In doctoral dissertation, we addressed the key challenges in the development of MNPs, including improvement of the MNP dispersion stability, drug loading into MNP shell, and MNP safety. To improve the physical stability of MNPs, we transformed MNP dispersions into a dry form, adopting the electrospinning method as an innovative approach to prepare a non-powdered product in the form of hydrophilic nanofibers with up to 65% (w/w) MNPs, which enabled rapid, easy, and efficient reconstitution of MNPs. Furthermore, we successfully incorporated four different drugs into hydrophilic nanofibers and demonstrated that their physicochemical properties significantly affect the nanofiber properties. We developed a drug-loading method for MNPs with a mesoporous silica shell and dry the prepared MNP formulation using electrospinning to prevent MNP aggregation and premature drug release from MNPs into the dispersion during storage. Thus, we managed to prepare homogenous nanofibers with ~20.0% (w/w) of MNPs and ~4.2% (w/w) of the drug. We conducted the first systematic evaluation of the influence of silica-coated MNP surface morphology on the biological response of cells in vitro and demonstrated that MNPs with smaller pore size on the surface are safer than MNPs with bigger pore size. With developed innovative technological approaches, we opened new possibilities for future investigations and addressed some crucial technological challenges in the development of nanoparticles. With our findings, we contributed our small piece to the mosaic of knowledge, which is crucial for ensuring safe, effective, and quality MNPs for use in various biomedical applications.

• Keywords: Bioevaluation, electrospinning, ibuprofen, magnetic nanoparticles, iron-oxide nanoparticles, nanofibers, polyethylene oxide, poloxamer 188, drying, theranostics, drug loading.