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Izolacija biopolimera fibroina in njegova uporaba v razvoju dostavnih sistemov za nadzorovano sproščanje estradiola
ID Križman, Kaja (Author), ID Kristl, Julijana (Mentor) More about this mentor... This link opens in a new window, ID Drnovšek, Nataša (Comentor)

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Abstract
V magistrski nalogi so predstavljene edinstvene lastnosti svile v platformi za načrtovanje in izdelavo zdravil z nadzorovanim sproščanjem. Veliko zanimanje za biopolimer fibroin izhaja iz redke kombinacije njegovih želenih lastnosti, kot so možnost izolacije in čiščenja z vodnim medijem, predelava v odsotnosti kemičnih premreževal, sterilizacija z različnimi metodami, itn. Kljub temu je potrebna obravnava kritičnih točk na poti do trženja fibroinskih izdelkov, da bi bila zagotovljena ustrezna kakovost, učinkovitost in varnost fibroinskega proizvoda. V eksperimentalnem delu naloge smo razvili robusten in razširljiv proces izolacije fibroina iz kokonov sviloprejke Bombyx mori in vzpostavili kontrolne korake za optimizacijo identitete in čistosti izdelka. Vrednotenje pripravljene raztopine fibroina je bila naša začetna točka v sistematičnem pristopu za razvoj formulacije. Vključeval je izbiro modelne zdravilne učinkovine estradiola in ugotavljanje kritičnih parametrov za enostavno pripravo fibroinskih dostavnih sistemov z nadzorovanim sproščanjem. Pripravili smo različne fibroinske dostavne oblike (filme, hidrogele, porozne liofilizate) z dodatkom etanola, ki je služil za raztapljanje estradiola in povečal hitrost geliranja raztopine fibroina. Potencial dostavnih sistemov estradiola smo opredelili s testiranjem vgrajevanja, sproščanja in vitro v fosfaten pufer brez in s površinsko aktivno snovjo ter analizo koncentracije estradiola s tekočinsko kromatografijo visoke ločljivosti. Lastnosti dostavnih sistemov in njihov vpliv na fibroin smo določili z uporabo različnih analitskih metod: vrstične elektronske mikroskopije, infrardeče spektroskopije s Fourierjevo transformacijo in rentgenske praškovne analize. Tanki filmi so se v pufru raztopili v petih minutah in sprostili estradiol, saj je bil v njih fibroin pretežno amorfen in vodotopen. Kemične in konformacijske lastnosti fibroina v tankih filmih se niso spremenile, kljub vključevanju estradiola v etanolni raztopini. Debelejši filmi so bili zaradi postopka geliranja fibroina z etanolom sami po sebi netopni in so posledično imeli večjo vsebnost kristaliničnih domen oz. β-ravnin. Za pripravo debelejših filmov smo vmesne hidrogelne oblike posušili. S testiranjem sproščanja estradiola in vitro smo ugotovili podaljšano sproščanje vse do 129 dni, kar potrjuje obetavno uporabo debelejših filmov z estradiolom. Porozni cilindri, pripravljeni z liofilizacijo, so kot dostavni sistemi manj primerni, ker je bil estradiol po vgrajevanju prisoten le na površini v obliki kristalov in ne v fibroinskem ogrodju.

Language:Slovenian
Keywords:Izolacija, biopolimer, fibroin, svila, dostavni sistem, nadzorovano sproščanje, estradiol, hormon
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2019
PID:20.500.12556/RUL-106420 This link opens in a new window
Publication date in RUL:22.02.2019
Views:1775
Downloads:242
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Secondary language

Language:English
Title:Isolation of silk fibroin biopolymer and development of delivery systems for controlled release of estradiol
Abstract:
This master thesis presents the unique properties of silk in the platform for the design and manufacture of controlled release medicines. A great deal of interest in the biopolymer fibroin derives from a rare combination of its properties, such as the possibility of isolation and aqueous-based purification, processing in the absence of chemical cross-linkers, sterilisation by various methods, etc. Nevertheless, critical points on the path to bringing fibroin-based products to the market, while ensuring proper quality, efficacy and safety remain to be considered. Within our experimental research, we developed a robust and scalable process of isolating fibroin from the cocoons of silkworm Bombyx mori and established control steps to optimise the identity and purity of the product. The characterisation of the prepared fibroin solution was our starting point in a systematic approach to formulation development, including the selection of estradiol as a drug candidate and determination of critical parameters for the preparation of fibroin delivery systems with controlled release. We prepared various fibroin delivery forms (films, hydrogels and porous scaffolds) with the addition of ethanol, which served to dissolve estradiol and accelerate the gelation of the fibroin solution. We determined the potential of estradiol delivery systems by testing the incorporation, in vitro release in the phosphate buffer without and with the surfactant and analysis of estradiol concentrations with high-performance liquid chromatography. The properties of our delivery systems and their influence on fibroin were determined with different analytical methods: scanning electron microscopy, Fourier-transform infrared spectroscopy and X-ray powder diffraction. Thin films were dissolved in the buffer within five minutes with initial “burst-release” of estradiol, as the fibroin in them was predominantly amorphous and water-soluble. Chemical and conformational properties of fibroin in thin films did not change, despite the incorporation of estradiol in ethanol solution. Thick films were inherently insoluble due to the gelation of fibroin with ethanol and consequently had a higher content of crystalline domains or β-sheets. For the preparation of thick films, we dried the intermediate hydrogel forms. By testing the release of estradiol in vitro, we found a prolonged release for up to 129 days, which confirms the promising use of the thick films with estradiol. Porous scaffolds prepared by lyophilisation are less suitable as delivery systems since estradiol was present only on the surface in the form of crystals and was not incorporated into the fibroin matrix.

Keywords:Isolation, biopolymer, fibroin, silk, delivery system, controlled release, estradiol, hormone

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