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Optimizacija izdelave liposomov z vitaminom C kot modelnega protirakavega dostavnega sistema
ID Peternel, Aleks (Author), ID Doljak, Bojan (Mentor) More about this mentor... This link opens in a new window, ID Pavlin, Mojca (Co-mentor)

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Abstract
Liposomi spadajo v kategorijo nanodelcev, za katere je značilno, da vsaj v eni dimenziji ne presegajo 100 nm. Liposomi so zlasti zanimivi kot dostavni sistemi za ciljanje z zdravilnimi učinkovinami. Aktivno ciljanje omogočajo specifični ligandi na površini liposomov, medtem ko je pasivno ciljanje, predvsem tumorjev, posredovano z učinkom povečane permeabilnosti in retencije. Liposomi so vezilki sferične oblike, ki nastanejo z upogibanjem amfifilnega lipidnega dvosloja ter pri tem ukleščijo del topila. Liposome kategoriziramo po številu koncentričnih notranjih membran - lamel. Liposomi lahko vežejo (enkapsulirajo) tako lipofilne, kot hidrofilne molekule, odvisno tudi od načina njihove priprave. V okviru magistrske naloge smo optimizirali izdelavo liposomov z želenimi lastnostmi (velikost, učinkovitost enkapsulacije, uporabnost kot dostavni sistem). Preverili smo, kako različni mehanski načini priprave (ekstruzija, sonikacija in filtracija) vplivajo na velikost liposomov. Najmanjše liposome smo pripravili z uporabo kombinacije vseh treh načinov, vendar smo zaradi težav s soniciranjem, za njihovo pripravo uporabljali kombinacijo ekstruzije s filtracijo. Z ekstruzijo dobimo majhne, unilamelne liposome, s filtracijo pa zožimo porazdelitev velikosti veziklov in dodatno zagotovimo sterilnost. Z modelno spojino fluoresceina smo optimizirali učinkovitost enkapsulacije liposomov, s spreminjanjem hitrosti vrtenja ter prenosa lipidne faze v vodno fazo. Največjo enkapsulacijo, ki je v povprečju znašala okrog 6 odstotek, smo dosegli z vrtenjem pri 800 obratih na minuto in prenosu, ki je skupno trajal 4 sekunde. Na podlagi optimiziranega protokola priprave, smo v liposome enkapsulirali vitamin C in jih kot dostavni sistem uporabili na celični liniji trojno negativnega raka dojk MDA-MB-231. V primerjavi s prostim vitaminom C (citotoksičnost nad 95 odstotek), je liposomska oblika vitamina C manj učinkovita. Celo prazni liposomi so bili bolj citotoksični kot liposomi z vitaminom C, učinek pa je verjetno posledica prisotnosti enkapsuliranega etanola.

Language:Slovenian
Keywords:Liposomi, izdelava, ekstruzija, sonikacija, fluorescein, vitamin C, MDA-MB-231
Work type:Master's thesis/paper (mb22)
Organization:FFA - Faculty of Pharmacy
Year:2019
Publication date in RUL:19.09.2019
Views:688
Downloads:294
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Secondary language

Language:English
Title:Production optimization of vitamin C-containing liposomes as a model anti-cancer delivery system
Abstract:
Liposomes are members of the nano-particle family and are characterized by at least one dimension not exceeding 100 nm. Liposomes are particularly interesting as drug targeting delivery systems. The active targeting is achieved using specific ligands on the surface of liposomes, while passive targeting, which exploits the enhanced permeability and retention effect, is used especially in tumours. Liposomes are spherical vesicles, consisting of a bent amphiphilic lipid bilayer that engulfs part of the solvent. There are several types of liposomes classified by the number of concentric inner membranes called lamellas. Liposomes are able to bind (encapsulate) both lipophilic and hydrophilic molecules, depending also on the technique, used in their preparation. In the course of the master's thesis we optimised the production of liposomes with desired characteristics (size, encapsulation efficiency, applicability as delivery system). We determined the effect of mechanical techniques of production (extrusion, sonication and filtration) on liposomal size. The smallest liposomes were prepared using the combination of all three techniques, but due to problems with sonication, the combination of extrusion with filtration was ultimately selected for their preparation. Extrusion produces unilamellar liposomes, while filtration gives narrower size distribution of the vesicles and additionally ensures sterility of the formulation. Fluorescein was used as a model substance for determining encapsulation efficiency by varying the speed of rotation and transfer of the lipid phase into the aqueous phase. The highest encapsulation, which was on average about 6 percent, was achieved at 800 turns per minute and the total transfer time of 4 seconds. Using the optimised preparation protocol, we encapsulated vitamin C into the liposomes and used them as a delivery system to the triple negative breast cancer MDA-MB-231 cell line. Compared to free vitamin C, which on average decreased cell viability more than 95 percent, the liposome formulation with vitamin C was not as cytotoxic. Even empty liposomes were more cytotoxic than liposomes containing vitamin C, the effect being probably attributable to the presence of encapsulated ethanol.

Keywords:Liposomes, production, extrusion, sonication, fluorescein, vitamin C, MDA-MB-231

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