Sintētiskie lipīdi uz 1,4-dihidropiridīnu bāzes - iegūšana, īpašību un iegūto liposomu raksturojums.
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Date
2022
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Rīgas Stradiņa universitāte
Rīga Stradiņš University
Rīga Stradiņš University
Abstract
Darba mērķis ir veikt nanodaļiņas raksturojošu parametru sakarību analīzi, veicot jaunu katjono 1,4-dihidropiridīnu pašasociācijas īpašību pārbaudi, raksturojot veidotās daļiņas, to stabilitāti. Darbā tiek meklēti savienojumi, kas spēj veidot stabilas liposomas. Līdzīgas liposomas var tikt izmantotas kā zāļu vielu, gēnu transporta formas cilvēka šūnās. Pateicoties ilggadējiem pētījumiem, šobrīd tās jau ir pierādījušas sevi SARS-CoV-2 vakcīnu sastāvā, kā mRNS nesējas. 1,4-DHP liposomas tiek uzskatītas par daudzsološām, taču tās vēl netiek izmantotas medicīnā kā zāļu transporta formas, jo nepieciešami vēl papildus pētījumi.
Darbā tika iegūti 7 sintētsiko lipīdu analogi, no kuriem 4 bija jauni, vēl nepētīti savienojumi, tiem tika veikta pilna fiziko-ķīmiskā analīze un pētītas to pašasociācijas jeb liposomas veidojošās īpašības. Jaunie savienojumi tiks pētīti tālāk. Tika noskaidrots, ka, lai arī visi savienojumi ir ļoti līdzīgi, to nelielās struktūras īpašības nozīmīgi maina to veidoto liposomu stabilitāti un īpašības. Lielākā daļa pētīto vielu veidoja stabilas liposomas ar vidējo diametru 100-200 nm. Tika parādīts, ka, pievienojot antracēna fragmentu katjonā lipīda molekulā, strukturāli līdzīgu savienojumu fluorescence tiek uzlabota 6 reizes.
The aim of the work is to analyze the relationships between the parameters characterizing nanoparticles by performing a test of the self-association properties of cationic 1,4-dihydropyridines, characterizing the formed particles and their stability. The work is looking for compounds that can form stable liposomes. Similar liposomes can be used as a mode of transport for drugs and genes in human cells. Liposomes have been fundamental in the development of the new SARS-CoV-2 vaccines, they are used as the transport systems of mRNA. 1,4-DHP liposomes are considered promising, but are not yet used in medicine as a form of drug delivery. Seven analogous synthetic lipids were obtained in the work, four of which were original new, as of yet unknown compounds, their physico-chemical analysis was performed and their self-assembling or liposome-forming properties were studied. The new compounds will be further studied. It was found that although all the compounds are very similar, their small differences in structure significantly alter the stability of the liposomes they form. Most of the compounds studied were stable liposomes with a mean diameter of 100-200 nm. The addition of an anthracene moiety to one of two very similar compounds was found to improve the fluorescence of the substance 6-fold.
The aim of the work is to analyze the relationships between the parameters characterizing nanoparticles by performing a test of the self-association properties of cationic 1,4-dihydropyridines, characterizing the formed particles and their stability. The work is looking for compounds that can form stable liposomes. Similar liposomes can be used as a mode of transport for drugs and genes in human cells. Liposomes have been fundamental in the development of the new SARS-CoV-2 vaccines, they are used as the transport systems of mRNA. 1,4-DHP liposomes are considered promising, but are not yet used in medicine as a form of drug delivery. Seven analogous synthetic lipids were obtained in the work, four of which were original new, as of yet unknown compounds, their physico-chemical analysis was performed and their self-assembling or liposome-forming properties were studied. The new compounds will be further studied. It was found that although all the compounds are very similar, their small differences in structure significantly alter the stability of the liposomes they form. Most of the compounds studied were stable liposomes with a mean diameter of 100-200 nm. The addition of an anthracene moiety to one of two very similar compounds was found to improve the fluorescence of the substance 6-fold.
Description
Farmācija
Pharmacy
Veselības aprūpe
Health Care
Pharmacy
Veselības aprūpe
Health Care
Keywords
amfifīlie 1, 4-dihidropiridīni, liposomas, DLS, fluorescence., amphiphilic 1, 4-dihydropyridines, liposomes, DLS, fluorescence