Stabilizacija retinil acetata z vgrajevanjem v hidrofilna nanovlakna

Pavšič, Urška (author), Temova Rakuša, Žane (mentor), Potrč, Tanja (comentor)

Vitamin A (retinol) je lipofilen vitamin, ki je ključnega pomena za vid, rast kosti, celično diferenciacijo ter celjenje ran. Njegova uporaba je močno razširjena v dermatologiji in kozmetologiji, kjer se večinoma uporablja v izdelkih proti gubam, aknam ter luskavici. Ker so retinol in njegovi derivati nestabilni zaradi različnih dejavnikov okolja, je v sklopu njihove formulacije pomembna tudi ustrezna stabilizacija (npr. z dodatkom antioksidantov ali s tehnološkimi pristopi). V okviru magistrske naloge smo se osredotočili na stabilizacijo retinilacetata, ki je obetavna, a manj raziskana oblika vitamina A. Za namen vrednotenja njegove stabilnosti smo uporabili predhodno razvito analizno metodo na osnovi tekočinske kromatografije visoke ločljivosti, ki smo jo najprej ustrezno ovrednotili. Z izvedbo stresnih testov smo ugotovili, da je retinilacetat zelo občutljiv na svetlobo, visok in nizek pH ter povišano temperaturo in oksidacijo, hkrati pa smo potrdili stabilnostno indikativnost analizne metode. Ker je bil glavni namen naloge izboljšati stabilnost retinilacetata z njegovo vgradnjo v hidrofilna nanovlakna, smo se najprej osredotočili na optimizacijo postopka izdelave nanovlaken z elektrostatskim sukanjem. Pri tem smo optimizirali pretok polimerne raztopine in električno napetost in ovrednotili stabilnost retinilacetata brez in z dodatkom stabilizatorjev (z butilhidroksitoluenom in vitaminom E) v 96-% etanolu, v polimerni raztopini in v izdelanih nanovlaknih. Ugotovili smo, da je retinilacetat v 96-% etanolu bolj stabilen, če ga shranjujemo pri nižjih temperaturah in zaščitenega pred svetlobo, medtem ko njegova koncentracija in prisotnost polimerov nista imeli značilnega vpliva. Z ustrezno zaščito vseh komponent procesa pred svetlobo in dodatkom obeh stabilizatorjev, še posebej z vitaminom E, smo uspeli optimizirati postopek vgradnje v nanovlakna (> 80-% delež vgradnje) in njihove morfološke lastnosti, ki smo jih ovrednotili s pomočjo vrstičnega elektronskega mikroskopa. Z optimiziranim postopkom smo izdelali nanovlakna z različno vsebnostjo retinilacetata (0,3–1,0 %) in vitamina E (0,3–1,0 %). Pri vrednotenju njihove stabilnosti pri različnih pogojih shranjevanja smo potrdili ključen vpliv svetlobe na stabilnost retinilacetata tudi v nanovlaknih in manjši vpliv vlage. Rezultati dolgoročnega testiranja stabilnosti izdelanih nanovlaken kažejo, da je izdelava nanovlaken obetaven pristop za stabilizacijo retinilacetata, saj je bila vsebnost retinilacetata po enem mesecu shranjevanja v nanovlaknih bistveno višja (približno 90-%) v primerjavi z izhodiščno polimerno raztopino (približno 50-%).

• Language: Slovenian
• Keywords: elektrostatsko sukanje, nanovlakna, retinilacetat, stabilnost, vitamin E
• Work type: Master's thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2026
• PID: 20.500.12556/RUL-187639
• Publication date in RUL: 12.09.2026

Secondary language

• Language: English
• Title: Stabilization of retinyl acetate by incorporation into hydrophilic nanofibers

Abstract

Vitamin A (retinol) is a lipophilic vitamin that is crucial for vision, bone growth, cell differentiation and wound healing. Its use is widespread in dermatology and cosmetology, where it is mainly used against wrinkles, acne and psoriasis. Since retinol and its derivatives are unstable due to various environmental factors, appropriate stabilization is also important in their formulation (e.g. by adding antioxidants or using technological approaches). As part of the master's thesis, we focused on the stabilization of retinylacetate, which is a promising but less studied vitamin A form. To evaluate its stability, we used a previously developed analysis method based on high-performance liquid chromatography, which we first properly evaluated. By performing stress tests, we found that retinylacetate is very sensitive to light, high and low pH, elevated temperature and oxidation, and also confirmed the stability-indicating nature of the analytical method. Since the main purpose of the thesis was to improve the stability of retinylacetate by incorporating it into hydrophilic nanofibers, we first focused on optimizing the process of manufacturing nanofibers by electrostatic spinning. In doing so, we optimized the flow rate of the polymer solution and the electrical voltage and evaluated the stability of retinylacetate without and with the addition of stabilizers (butylhydroxytoluene and vitamin E) in 96% ethanol, in the polymer solution and nanofibers. We found that retinylacetate in 96% ethanol is more stable if stored at lower temperatures and protected from light, while its concentration and the presence of polymers had no significant effect. By protecting all process components from light and adding both stabilizers, especially vitamin E, we managed to optimize the process of incorporation into nanofibers, with > 80% retinylacetate incorporation and their morphological properties, which were evaluated using a scanning electron microscope. Using the optimized process, we produced nanofibers with different retinylacetate (0.3–1.0%) and vitamin E (0.3–1.0%) contents. When evaluating their stability under different storage conditions, we confirmed the key influence of light on the stability of retinylacetate also in nanofibers and a lesser influence of moisture. The results of long-term stability testing of the produced nanofibers show that the production of nanofibers is a promising approach for stabilizing retinylacetate, as the retinylacetate concentration in nanofibers was significantly higher (approximately 90%) after one month of storage compared to the starting polymer solution (approximately 50%).

• Keywords: electrospinning, nanofibers, retinylacetate, stability, vitamin E