Vpliv formulacijskih in procesnih dejavnikov na lastnosti nanostrukturiranih lipidnih nosilcev s kurkuminom

Marinič, Nina (avtor), Zupančič, Špela (mentor), Zidar, Anže (komentor)

Z razvojem nanodostavnih sistemov lahko izboljšamo delovanje spojin z omejeno topnostjo, nizko stabilnostjo in slabo biološko uporabnostjo. Mednje sodi tudi kurkumin, za katerega se pogosto raziskujejo lipidni nanodostavni sistemi. Ti zaradi dobre biokompatibilnosti in zmožnosti učinkovite vgradnje hidrofobnih molekul predstavljajo obetaven pristop za izboljšanje njegove biološke uporabnosti. V okviru magistrske naloge smo zato kurkumin v kombinaciji z rafiniranim oljem alg, bogatim z dokozaheksaenojsko kislino, vgrajevali v nanostrukturirane lipidne nosilce (NLC). NLC smo pripravili z metodo spreminjanja enega dejavnika naenkrat, s katero smo preučevali vpliv različnih formulacijskih parametrov, kot so vrsta in koncentracija lipidov, stabilizatorja, fosfolipida ter delež kurkumina v lipidni fazi. Po optimizaciji formulacije smo ovrednotili še vpliv procesnih parametrov vroče homogenizacije in ultrazvočne obdelave, vključno s hitrostjo in časom homogenizacije ter amplitudo, trajanjem in pulznim režimom soniciranja. Vplive homogenizacije smo dodatno preverili tudi z metodo načrtovanja eksperimentov. Pripravljenim vzorcem smo določali velikost delcev, polidisperzni indeks (PI), zeta potencial, učinkovitost vgrajevanja, učinkovitost procesa in kapaciteto vgrajevanja. Na podlagi rezultatov smo uspešno oblikovali optimizirano formulacijo NLC, ki je vsebovala Compritol 888 ATO in olje alg v razmerju 3 : 2, fosfolipid PEG 2000 DSPE ter Poloxamer 188 kot stabilizator. Razvoj formulacije je temeljil na zahtevah po velikosti delcev pod 200 nm, homogeni populaciji s PI pod 0,3, stabilnem zeta potencialu (≥ |20| mV) ter visoki stopnji vgrajevanja kurkumina v lipidno ogrodje. Stabilnost optimiziranih NLC smo spremljali 70 dni in jo primerjali s stabilnostjo večjih NLC, ki so imeli povprečno velikost ~ 230 nm. Obe formulaciji sta bili stabilni, pri čemer so večji NLC bolje ohranjali fizikalne lastnosti, manjši pa vgrajeni kurkumin. Preverili smo tudi stabilnost liofiliziranih vzorcev, vendar je odsotnost krioprotektantov povzročila agregacijo delcev in povečanje velikosti ter PI po redispergiranju.

• Jezik: Slovenski jezik
• Ključne besede: nanodostavni sistemi, nanostrukturirani lipidni nosilci, kurkumin, stabilnost, učinkovitost vgrajevanja
• Vrsta gradiva: Magistrsko delo/naloga
• Organizacija: FFA - Fakulteta za farmacijo
• Leto izida: 2026
• PID: 20.500.12556/RUL-189842
• Datum objave v RUL: 17.10.2026

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Influence of formulation and process parameters on the properties of curcumin-loaded nanostructured lipid carriers

Izvleček

The development of nanodelivery systems can enhance the performance of compounds with limited solubility, low stability and poor bioavailability. Curcumin is one such compound, for which lipid-based nanodelivery systems are widely investigated. Their good biocompatibility and ability to efficiently encapsulate hydrophobic molecules make them a promising approach to improving its bioavailability. In this master’s thesis, curcumin combined with refined algal oil rich in docosahexaenoic acid was incorporated into nanostructured lipid carriers (NLC). The NLC were prepared using a one‑factor‑at‑a‑time approach to investigate the influence of formulation parameters, including the type and concentration of lipids, stabilizer, phospholipid and curcumin content in the lipid phase. After optimizing the formulation, we evaluated the effects of hot homogenization and ultrasonication parameters, such as homogenization speed and time, as well as sonication amplitude, duration and pulsed mode. The impact of homogenization was further examined using a design of experiments approach. The prepared samples were characterized for particle size, polydispersity index (PI), zeta potential, encapsulation efficiency, process efficiency and loading capacity. Based on the obtained results, an optimized NLC formulation was successfully developed, consisting of Compritol® 888 ATO and algal oil in a 3:2 ratio, together with the phospholipid PEG 2000 DSPE and Poloxamer 188 as the stabilizer. The development of the formulation was guided by requirements for particle size below 200 nm, a homogeneous particle population with a PI below 0.3, a stable zeta potential (≥ |20| mV), and a high curcumin entrapment efficiency within the lipid matrix. The stability of the optimized NLC was monitored over 70 days and compared with that of larger NLC with an average particle size of ~230nm. Both formulations remained stable, with the larger NLC better preserving their physicochemical properties, while the smaller NLC retained the encapsulated curcumin more effectively. We also tested the stability of lyophilized samples, but the absence of cryoprotectants resulted in particle aggregation and an increase in size and PI after redispersion.

• Ključne besede: nanodelivery systems, nanostructured lipid carriers, curcumin, stability, encapsulation efficiency