Razvoj trdnih lipidnih nanodelcev z reducirano obliko koencima Q10 za dermalno uporabo

Jevnikar, Lana (author), Kocbek, Petra (mentor), Roškar, Robert (co-mentor)

Nanotehnologija ima že vrsto let pomembno vlogo pri izdelavi kozmetičnih izdelkov. Z odkritjem trdnih lipidnih nanodelcev se je v kozmetiki pojavila možnost vgrajevanja predvsem lipofilnih kozmetično aktivnih sestavin vanje. Vgrajene v lipidne nanodelce lahko takšne kozmetično aktivne sestavine prodrejo globlje v kožo, se sproščajo skozi daljši čas in so bolj stabilne. Med tovrstne kozmetično aktivne sestavine spada tudi koencim Q10, ki je postal pomembna sestavina kozmetičnih izdelkov proti staranju kože. V trdne lipidne nanodelce običajno vgrajujemo oksidirano obliko koencima Q10, ki se po dermalni uporabi v koži pretvori v reducirano obliko, ki ima antioksidativno delovanje. Glavni cilj diplomske naloge je bil izdelati stabilno disperzijo trdnih lipidnih nanodelcev z vgrajeno reducirano obliko Q10. Ker je bil koencim Q10 komercialno dostopen v oksidirani obliki, smo se najprej osredotočili na pripravo reduciranega koencima Q10. Postopek redukcije smo optimizirali s prilagajanjem koncentracije vhodnega koencima Q10, mase reducenta NaBH4 in ostalih parametrov. Z metodo tekočinske kromatografije visoke ločljivosti smo vrednotili vsebnost obeh oblik koencima Q10 v vzorcu po redukciji ter določali uspešnost redukcije. Le-ta je bila uspešna, če smo dosegli vsaj 95 % delež reduciranega koencima Q10. Dokazali smo ustreznost metode priprave vzorca trdnih lipidnih nanodelcev za analizo s tekočinsko kromatografijo visoke ločljivosti ter ugotovili, da pride do izgub koencima Q10 med izdelavo trdnih lipidnih nanodelcev, a vzroka nismo uspeli identificirati. Po izdelavi trdnih lipidnih nanodelcev z metodo soniciranja taline lipida v vodno fazo stabilizatorja smo vrednotili njihove fizikalne lastnosti. Ugotovili smo, da je povprečna velikost trdnih lipidnih nanodelcev brez učinkovine 132,7 nm, po vgradnji kozmetično aktivne sestavine in dodatku hidrofilnega antioksidanta v disperzijo pa je bila velikost večja, a še vedno v nanometrskem območju. Njihov zeta potencial je bil manj negativen, kar kaže na slabšo elektrostatsko stabilizacijo disperzije trdnih lipidnih nanodelcev. Zaključimo lahko, da nismo uspeli izdelati stabilne disperzije trdnih lipidnih nanodelcev z vgrajeno reducirano obliko koencima Q10, smo pa uspešno reducirali komercialno dostopen koencim Q10 in dokazali, da pride do izgub koencima Q10 med izdelavo trdnih lipidnih nanodelcev. Pri reducirani obliki Q10 je vzrok za neuspešno vgradnjo verjetno njena nestabilnost, medtem ko pri oksidirani obliki Q10 vzroka za nizko vgradnjo nismo ugotovili.

• Language: Slovenian
• Keywords: koencim Q10, trdni lipidni nanodelci, stabilnost, antioksidanti
• Work type: Bachelor thesis/paper
• Organization: FFA - Faculty of Pharmacy
• Year: 2020
• PID: 20.500.12556/RUL-119771
• Publication date in RUL: 11.09.2020

Secondary language

• Language: English
• Title: Development of solid lipid nanoparticles with reduced form of coenzyme Q10 for dermal application

Abstract

Nanotechnology plays an important role in production of modern cosmetic products. The discovery of solid lipid nanoparticles opened the possibility of incorporating mainly lipophilic cosmetically active ingredients in them. Cosmetically active ingredients incorporated in solid lipid nanoparticles can penetrate deeper into the skin, be released over a longer period of time and are more stable. Coenzyme Q10 is a cosmetically active ingredient, important in anti-aging skincare. It is usually incorporated into solid lipid nanoparticles in its oxidized form and converted to a reduced form which has antioxidant activity after dermal application. The aim of this thesis was to produce a stable dispersion of solid lipid nanoparticles with incorporated reduced form of coenzyme Q10. Coenzyme Q10 was commercially available only in its oxidized form so we first focused on preparation of the reduced form of coenzyme Q10. We optimized the reduction process by adjusting the starting concentration of coenzyme Q10 and the mass of reducing agent NaBH4, as well as several other reaction parameters. The content of both forms of coenzyme Q10 in the sample after the reduction process was evaluated by high-performance liquid chromatography. The reduction was considered as successful if the sample consisted of at least 95% of the reduced form of coenzyme Q10. We confirmed the suitability of the method used for preparation of a sample of solid lipid nanoparticles for analysis with high-performance liquid chromatography. We demonstrated that coenzyme Q10 was lost during the preparation of solid lipid nanoparticles, but the reason has not been identified. Solid lipid nanoparticles were produced by sonification of the melted lipid into the aqueous phase with the stabilizer and their physical properties were evaluated afterwards. The average size of solid lipid nanoparticles without the active ingredient was 132.7 nm. In the samples where coenzyme Q10 and hydrophilic antioxidant were added the average size of solid lipid nanoparticles was significantly increased but it was still in nanometer range. Zeta potential of solid lipid nanoparticles with coenzyme Q10 was less negative compared to the control sample, indicating poorer electrostatic stabilization of the dispersion of these solid lipid nanoparticles. We can conclude that preparation of of solid lipid nanoparticles with incorporated reduced form of coenzyme Q10 was not sucessful. However, we successfully reduced commercially available coenzyme Q10 and demonstrated that the reason for low incorporation of reduced coenzyme Q10 in nanoparticles was its loss during the preparation of solid lipid nanoparticles. The reason is probably its instability, whereas the reason for low incorporatin of the oxidized form of coenzyme Q10 was not identified.

• Keywords: coenzyme Q10, solid lipid nanoparticles, stability, antioxidants