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Razvoj lipidnih nanodelcev za dostavo adjuvansa za cepiva
ID Cvikl, Mojca (Author), ID Kocbek, Petra (Mentor) More about this mentor... This link opens in a new window, ID Potrč, Tanja (Comentor)

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Abstract
Razvoj nanodelcev je v zadnjih letih doživel velik napredek na področju medicine, s poudarkom na ciljani dostavi zdravilnih učinkovin in cepiv. Z namenom doseganja večje učinkovitosti cepiv in dolgoročne zaščite pred patogeni v cepiva dodajamo adjuvanse, med katerimi se danes največkrat uporabljajo aluminijeve soli in agonisti receptorjev za prepoznavanje vzorcev. Za dostavo adjuvansov v telo so razvili različne nanodostavne sisteme, med njimi veliko obetajo lipidni nanodelci, saj omogočajo ciljano dostavo vgrajenih učinkovin in njihovo izboljšano stabilnost in vivo. Cilj magistrske naloge je bil izdelati fizikalno stabilno disperzijo lipidnih nanodelcev (trdni lipidni nanodelci in nanostrukturirani lipidni nosilci) z vgrajenim adjuvansom SG11 s pomočjo metode soniciranja taline lipida v vodno raztopino stabilizatorjev. Optimizirali smo pogoje izdelave lipidnih nanodelcev s ciljem izdelati nanodelce s povprečno velikostjo < 200 nm in ozko porazdelitvijo velikosti. Izdelanim disperzijam smo merili povprečni premer delcev, polidisperzni indeks in zeta potencial. Te lastnosti smo spremljali do 60 dni od izdelave z namenom ugotavljanja fizikalne stabilnosti nanodelcev, izdelanih in shranjenih pri različnih pogojih. Za izdelavo nanodelcev z adjuvansom za cepiva smo uporabili različne medije (prečiščena voda, fosfatni pufer) in organska topila (etanol, tetrahidrofuran) ter jih shranjevali pri različnih pogojih (v hladilniku, v zamrzovalniku). Ugotovili smo, da so nanodelci shranjeni v hladilniku fizikalno stabilnejši od tistih, shranjenih v zamrzovalniku. Za določanje vsebnosti adjuvansa v disperziji lipidnih nanodelcev smo uporabili metodo tekočinske kromatografije visoke ločljivosti. Rezultati so potrdili učinkovito vgradnjo adjuvansa v lipidne nanodelce. Na podlagi meritev vsebnosti adjuvansa v nanodelcih po 60 dneh od izdelave smo ugotovili, da je pri nekaterih vzorcih prišlo do »odpuščanja« adjuvansa iz delcev. Kot topilo za vgradnjo adjuvansa v nanodelce se je bolje izkazal etanol kot tetrahidrofuran. Z uporabo fosfatnega pufra kot disperznega medija smo želeli pripraviti disperzije nanodelcev, biokompatibilne s celicami. Rezultati so pokazali, da je bila disperzija nanodelcev fizikalno stabilnejša, če smo za njeno izdelavo in redispergiranje nanodelcev uporabili raztopino stabilizatorjev v fosfatnem pufru kot če smo uporabili sam fosfatni pufer.

Language:Slovenian
Keywords:adjuvans, cepiva, fizikalna stabilnost, lipidni nanodelci, nanodostavni sistemi
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2024
PID:20.500.12556/RUL-158518 This link opens in a new window
Publication date in RUL:14.06.2024
Views:268
Downloads:60
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Secondary language

Language:English
Title:Development of lipid nanoparticles for delivery of vaccine adjuvant
Abstract:
The development of nanoparticles has seen great progress in recent years in the field of medicine, focusing on targeted delivery of drugs and vaccines. In order to achieve greater vaccine efficacy and provide long-term protection against pathogens, adjuvants are added to vaccines, with aluminum salts and pattern-recognition receptor agonists, being the most commonly used nowadays. Various nanodelivery systems have been developed for adjuvant delivery, among which lipid nanoparticles show great promise as they allow targeted delivery and improved stability of incorporated active ingredients in vivo. The aim of this master's thesis was to produce physically stable dispersion of lipid nanoparticles (solid lipid nanoparticles and nanostructured lipid carriers) with incorporated adjuvant SG11 by sonication of melted lipid into aqueous solution of stabilizers. We optimized the conditions for the production of lipid nanoparticles with the goal of producing nanoparticles with an average size < 200 nm and a narrow particle size distribution. The dispersions were characterized by measuring the average particle diameter, polydispersity index and zeta potential. These properties were monitored for up to 60 days after production to assess the physical stability of nanoparticles and stored under different storage conditions. Different media (purified water, phosphate buffer) and organic solvents (ethanol, tetrahydrofuran) were used to produce vaccine adjuvant loaded nanoparticles, which were stored under different conditions (in refrigerator, in freezer). Nanoparticles stored in the refrigerator were found to be more physically stable than those stored in the freezer. High-performance liquid chromatography was used to determine the adjuvant content in the lipid nanoparticle dispersion. The results confirmed the efficient incorporation of the adjuvant into the lipid nanoparticles. Based on measurements of adjuvant content in nanoparticles after 60 days from production, we found that in some samples, there was a »leakage« of the adjuvant from the particles. Ethanol proved to be a better solvent for adjuvant incorporation into nanoparticles compared to tetrahydrofuran. By using phosphate buffer as a dispersion medium, we aimed to prepare nanoparticle dispersions, biocompatible with cells. The results showed that nanoparticle dispersion was physically more stable when a solution of stabilizers in phosphate buffer was used for its production and redispersion of nanoparticles compared to phosphate buffer used alone.

Keywords:adjuvant, vaccines, physical stability, lipid nanoparticles, nanodelivery systems

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