20.500.12556/RUL-184328 Vrednotenje vpliva volumna disperzije in dodatka sladkorjev na lastnosti liposomov pred in po sušenju z razprševanjem The influence of dispersion volume and addition of sugars on liposome characteristics before and after spray drying Liposomi so lipidni dostavni sistemi, ki lahko izboljšajo dostavo in biološko uporabnost vgrajenih učinkovin, zlasti tistih s slabšo topnostjo v vodi. Kljub temu pa je ena od slabosti liposomov omejena fizikalna in kemijska stabilnost v vodni disperziji. Obstojnost lahko podaljšamo s pretvorbo disperzije v suho obliko s sušenjem z razprševanjem, pri tem pa dodamo sladkorje, ki delujejo kot zaščitna sredstva. Liposome smo pripravili iz hidrogeniranega sojinega fosfatidilholina in holesterola po metodi tankih filmov. Preučevali smo, ali je njihovo pripravo mogoče prenesti iz manjšega v petkrat večje merilo ob ohranjenih razmerjih vhodnih sestavin, nato pa jih ob uporabi laktoze, trehaloze ali saharoze pretvoriti v stabilen suh prašek s sušenjem z razprševanjem. Liposome smo ovrednotili pred sušenjem in po njem z določanjem velikosti veziklov, polidisperznega indeksa in potenciala zeta, velikostno porazdelitev suhih delcev pa z lasersko difrakcijo. Povečanje merila ni bistveno spremenilo lastnosti veziklov, kar potrjuje uspešnost prenosa postopka. Disperzije so kljub skoraj nevtralnemu površinskemu naboju ostale fizikalno stabilne tudi po 24 urah. Med tremi preizkušenimi sladkorji sta laktoza in trehaloza zagotovili dobro zaščito veziklov med sušenjem, saj so se liposomi po rekonstituciji vrnili v nanometrsko območje z ozko porazdelitvijo velikosti. Saharoza se je pri uporabljenih pogojih sušenja izkazala za neustrezno, kar pripisujemo njeni nižji temperaturi steklastega prehoda v primerjavi z drugima sladkorjema. Kot najustreznejše razmerje med lipidi in sladkorjem smo določili razmerje 1:10. V nadaljevanju smo kot modelno učinkovino v liposome vgradili resveratrol, lipofilni polifenol s slabo topnostjo. Njegova vgradnja ni bistveno spremenila velikosti veziklov, najvišji izkoristek sušenja in najnižji polidisperzni indeks po rekonstituciji pa je dala formulacija s trehalozo. Z rezultati smo potrdili, da je liposome mogoče pripraviti v petkrat večjem merilu in jih s sušenjem z razprševanjem pretvoriti v stabilno suho obliko z ohranjenimi lastnostmi veziklov po rekonstituciji, pri čemer se pri enakih pogojih sušenja vsi sladkorji ne izkažejo enako ustrezni. Liposomes are lipid-based delivery systems that can improve the delivery and bioavailability of incorporated drugs, particularly those with poor water solubility. One of the drawbacks, however, is the limited physical and chemical stability of liposomes in aqueous dispersions. Their stability can be improved by converting them into a dry form by spray drying, with the addition of sugars as protective agents. Liposomes were prepared from hydrogenated soy phosphatidylcholine and cholesterol using the thin-film method. Our goal was to investigate whether the preparation could be transferred from a small scale to a five-fold larger scale while maintaining the ratios of the input components before converting the dispersions into a stable dry powder by spray drying using lactose, trehalose, or sucrose. Liposomes were evaluated before and after drying by measuring vesicle size, polydispersity index, and zeta potential, while the size distribution of the dry particles was determined by laser diffraction. Scaling up did not substantially alter the properties of the vesicles, confirming the successful transfer of the procedure. Despite their nearly neutral surface charge, the dispersions remained physically stable for at least 24 hours. Among the three tested sugars, lactose and trehalose provided good protection of the vesicles during spray drying, as the liposomes returned to the nanometre range with narrow size distribution after reconstitution. Sucrose proved unsuitable under the drying conditions used, which we attribute to its lower glass transition temperature compared with the other two sugars. The lipid-to-sugar ratio of 1:10 was determined to be the most suitable. Subsequently, resveratrol, a lipophilic polyphenol with poor water solubility, was incorporated into the liposomes as a model drug. Its incorporation did not substantially change the vesicle size, while the trehalose formulation provided the highest drying yield and the lowest polydispersity index after reconstitution. The results confirmed that liposomes can be prepared on a five-fold larger scale and converted by spray drying into a stable dry form with preserved vesicle properties after reconstitution, although not all sugars proved equally suitable under identical drying conditions. liposomi metoda tankih filmov sušenje z razprševanjem zaščitni sladkorji resveratrol povečanje merila liposomes thin-film method spray drying protective sugars resveratrol scale-up true false false [M. Voušek] Slovenski jezik Angleški jezik Magistrsko delo/naloga 2026-07-04 08:45:07 2026-07-04 08:45:21 2026-07-16 14:30:46 0000-00-00 00:00:00 2026 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 1970-01-01 577.352(043.2) 125634 283889155 32325.pdf 32325.pdf 1 1BF63A8946BA17A6B3099D934301A8AF 90a537f89db87fda940687b647e4e9752f8885785c9b9cc32e19df5f728a4eca d226fa59-7773-11f1-9b0d-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=237008 Fakulteta za farmacijo 0 0 0