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Title:Formation, characterization and application of polysaccharide aerogels
Authors:Horvat, Gabrijela (Author)
Knez, Željko (Mentor) More about this mentor... New window
Novak, Zoran (Co-mentor)
Files:.pdf DOK_Horvat_Gabrijela_2018.pdf (5,84 MB)
MD5: 4C82D8FEA5C023E260F5847416A6A8DE
 
Language:English
Work type:Doctoral dissertation (mb31)
Typology:2.08 - Doctoral Dissertation
Organization:FKKT - Faculty of Chemistry and Chemical Engineering
Abstract:The aim of this PhD dissertation was to describe and analyze the preparation and characterization of polysaccharide aerogels and their future pharmaceutical and medical application. For the research, we used four types of polysaccharides: pectin, alginate, xanthan and guar. We used two types of pectin, high-methoxyl and low-methoxyl pectin, because of their different gelation mechanisms. The first part of the dissertation describes the preparation and characterization of pure polysaccharide aerogels. First, we prepared pectin spherical aerogels, cross-linked with three different ions, and we investigated their final properties. Later, we developed a new method for the preparation of alginate, pectin, xanthan and guar aerogels. We used only ethanol and no other cross-linkers. Ethanol was removed in the later processes of supercritical drying, and the remaining final material was thus only porous polysaccharide. By this method, we were able to prepare pure xanthan and guar aerogels. Prior to this study, xanthan and guar aerogels were prepared only as composites. Pectin aerogels prepared by the new method have amazing properties. On the other hand, alginate aerogels show poor characteristics, and thus the methods need to be optimised. We tried different alginate viscosities, different alcohols (methanol, ethanol, 1-propanol and 1-butanol), and we investigated longer (24h) and shorter (1h) gel setting times. The second part of this dissertation describes the pharmaceutical and medical applications of prepared aerogels. The release of diclofenac sodium from spherical pectin aerogels was investigated in vitro. Calcium cross-linked aerogels were not able to retain the drug, and its release was immediate. In order to achieve controlled release of diclofenac sodium, zinc ions had to be used as cross-linkers. Later, a low water-soluble drug, nifedipine, was used as a model drug for the monolithic aerogels prepared by the new method. The release of nifedipine from pectin and alginate aerogels was highly increased, compared to the crystalline drug. This result is promising for future evaluation of these materials for increasing the bioavailability of poorly water-soluble drugs. Nifedipine release from xanthan and guar aerogels was prolonged up to two weeks. This result reveals a new perspective on such materials for their potential use in medicine as implants and local drug delivery. According to these results, we then developed a new coating material for medical-grade stainless steel from xanthan and pectin. An aerogel coating was loaded with diclofenac sodium and indomethacin, and their release profiles were investigated in vitro. Electrochemical analysis and cell tests proved the safety of such materials for use in medicine. Using aerogel coatings, the drug can be introduced locally into the body; therefore, the need for intravenous, post-operational treatment is greatly reduced.
Keywords:polysaccharides, aerogels, supercritical drying, drug carriers
Year of publishing:2018
Publisher:[G. Horvat]
Source:Maribor
UDC:544.774.2:54-139(043.3)
COBISS_ID:21321750 New window
NUK URN:URN:SI:UM:DK:NWXTJCBK
Views:885
Downloads:185
Metadata:XML RDF-CHPDL DC-XML DC-RDF
Categories:KTFMB - FKKT
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Secondary language

Language:Slovenian
Title:Priprava, karakterizacija in aplikacija polisaharidnih aerogelov
Abstract:Cilj doktorske dizertacije je priprava, karakterizacija in aplikacija polisaharidnih aerogelov. Za pripravo aerogelov smo uporabili štiri polisaharide: pektin, alginat, ksantan in guar. Uporabili smo dve vrsti pektina, visokometilirani in nizkometilirani pektin, ki se med seboj razlikujeta po stopnji esterifikacije ter s tem tudi po načinu geliranja. V prvem delu raziskave smo se osredotočili na pripravo in karakterizacijo polisaharidnih aerogelov. Najprej smo pripravili pektinske aerogele ter preiskovali vpliv ionov na geliranje ter končne lastnosti materialov. Razvili smo enotno metodo za pripravo alginatnih, pektinskih, ksantan in guar aerogelov z dodatkom etanola ter brez dodatnih zamreževalcev. Prvič smo opisali pripravo čistih ksantan in guar aerogelov, ki so do sedaj bili pripravljeni samo kot kompoziti. Z novo metodo smo dosegli izjemne lastnosti pektinskih aerogelov. Pripravo alginatnih aerogelov smo zaradi slabših strukturnih lastnosti optimizirali. Tako smo uporabili tri različne viskoznosti alginata, metanol, etanol, 1-propranol in 1-butanol ter primerjali krajši (1 h) ter daljši (24 h) čas geliranja. V drugem delu doktorske dizertacije smo raziskovali uporabo pripravljenih aerogelov kot nosilcev aktivnih učinkovin. Primerjali smo sproščanje doklofenak natrija iz pektinskih aerogelov, zamreženih z različnimi ioni in ugotovili, da je zamreževanje s kalcijem primerno, če želimo doseči takojšnje sproščanje učinkovine. Če želimo doseči podaljšano sproščanje, je primernejše zamreženje pektina s cinkovimi ioni. V nadaljevanju študije smo uporabili v vodi slabo topno učinkovino, nifedipin, ter jo vezali v monolitne polisaharidne aerogele, pripravljene po novi metodi. Ti nosilci so primerni za farmacevtske aplikacije, saj so pripravljeni samo iz polisaharida, brez dodatnih zamreževalcev. Tako je potencialni nosilec samo polisaharid v obliki visoko porozne strukture. Ugotovili smo, da se sproščanje nifedipina znatno poviša z vezavo na pektinske in alginatne aerogele v primerjavi s čisto učinkovino. Tako lahko dosežemo dosti višjo učinkovitost v vodi slabo topnih aktivnih učinkovin. Z vezavo na ksantan in guar aerogele je bilo sproščanje te učinkovine podaljšano do dveh tednov. Ta rezultat daje priložnost za aplikacijo takih aerogelov v medicini, morebiti za implantate ali za lokalno dostavo zdravil. V zadnjem delu smo pripravili kompozitni ksantan-pektin aerogel v obliki prevleke na jeklo. Primerjali smo sproščanje dveh aktivnih učinkovin, indometacina ter diklofenak natrija. Elektrokemijske ter celične študije so potrdile varnost uporabe takih nosilcev v medicini. Z aerogelnimi prevlekami dosežemo direktni vnos zdravila na željeno mesto v telesu ter tako preprečimo kasnejša vnetja in bolečine, predvsem pa znižamo potrebo po intravenskem vnosu zdravil po operativnih posegih. Sproščanje obeh učinkovin iz ksantan-pektin aerogelov je bilo podaljšano do 6 h.
Keywords:polisaharidi, aerogeli, superkritično sušenje, nosilci zdravilnih učinkovin


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