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Razvoj in fizikalno vrednotenje hidrogelov za tvorbo dermalnih filmov iz nanoceluloze z betametazondipropionatom
ID Milković, Sara (Author), ID Gosenca Matjaž, Mirjam (Mentor) More about this mentor... This link opens in a new window, ID Bolko Seljak, Katarina (Co-mentor)

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Abstract
Atopijski dermatitis (AD) je nenalezljiva, kronična vnetna bolezen kože, ki prizadene 10–30 % otrok in 2–10 % odraslih. Atopijska koža je suha in občutljiva, spremlja jo srbenje. Poškodbe kožne bariere, značilne za AD, nastanejo pod vlivom prepleta genetskih, okoljskih in vnetnih dejavnikov. Pomembno vlogo pri obvladovanju AD ima vsakodnevna nega kože ter izogibanje alergenom in sprožilcem vnetja, ki lahko poslabšajo stanje, pri zdravljenju pa v prvi vrsti uporabljamo lokalno protivnetno terapijo, pri hujših oblikah tudi sistemsko terapijo. Poleg konvencionalnih dermalnih farmacevtskih oblik se za zdravljenje AD raziskuje tudi uporaba hidrogelov. Slednje definiramo kot tridimenzionalne strukture polimernih verig t. i. tvorilcev gela, ki imajo sposobnost nabrekati in znotraj svojega ogrodja zadržati večje količine vode. V okviru magistrske naloge smo razvijali in vrednotili hidrogele na osnovi nanokristalne celuloze (NCC) dveh različnih proizvajalcev, ki sta se razlikovali tudi v makroskopskem videzu (tj. gelska ali praškasta NCC). Poleg NCC so hidrogele sestavljali tudi eden izmed treh različnih naravnih polimerov (alginat, pektin ali nizko viskozni hitosan), glicerol in betametazondipropionat (BDP) kot modelna zdravilna učinkovina (ZU), ki se sicer uporablja za zdravljenje AD. Najprej smo se osredotočili na optimizacijo vgradnje BDP v obliki samo-mikroemulgirajočega sistema (SMES) v hidrogele. Z metodo diferenčne dinamične kalorimetrije (DSC) smo potrdili, da je v hidrogele vgrajena ZU raztopljena. Z reološkimi meritvami smo ovrednotili vpliv dveh različnih NCC in SMES na viskoznost in amplitudno ter frekvenčno odvisnost elastičnega in plastičnega modula. Ugotovili smo, da NCC v obliki praška tvori bolj viskozne hidrogele, medtem ko dodatek SMES (z ali brez vgrajenega BDP) lahko ali zviša ali zniža viskoznost hidrogela oziroma vrednosti enega ali obeh modulov, odvisno od uporabljenega naravnega polimera in NCC. Nadalje smo iz hidrogelov z vgrajenim SMES (z in brez BDP) z metodo izhlapevanja topila pripravili filme. Pripravljeni filmi so izkazali nizko vsebnost zaostale vlage (do 2,15 % m/m), njihova debelina pa je znašala največ 0,090 ± 0,007 mm. Pripravljeni filmi so izkazali statistično značilno razliko v sposobnosti zadrževanja vode po namestitvi na membrano iz celuloznega acetata. Izdelani hidrogeli so se izkazali kot potencialni dostavni sistemi za BDP pri zdravljenju AD.

Language:Slovenian
Keywords:atopijski dermatitis, hidrogeli, kserogeli, nanokristalna celuloza, betametazondipropionat
Work type:Master's thesis/paper
Organization:FFA - Faculty of Pharmacy
Year:2021
PID:20.500.12556/RUL-127014 This link opens in a new window
Publication date in RUL:13.05.2021
Views:790
Downloads:210
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Secondary language

Language:English
Title:Development and physical evaluation of nanocellulose-based film-forming hydrogels containing betamethasone dipropionate
Abstract:
Atopic dermatitis (AD) is a non-contagious chronic inflammatory skin disease with the lifetime prevalence estimated to be 10–30 % in children and 2–10 % in adults. Atopic skin is characterised as dry and sensitive, accompanied by itch. Skin barrier dysfunction, distinctive in AD, occur under the influence of a mix of genetic, environmental and inflammatory factors. Daily skin care routine and the avoidance of allergens and the inflammation triggers that can worsen the condition have important role in the management of AD, while in the treatment, initially local anti-inflammatory therapy, and in severe AD, also systemic therapy is used. In addition to conventional dermal pharmaceutical forms, the use of hydrogels is also being investigated for the treatment of AD. Hydrogels are defined as three dimensional polymeric networks of gelling agents with the ability of swelling and holding a large quantity of water within its scaffold. Within the master's thesis hydrogels based on nanocrystalline cellulose (NCC) from two different manufacturers, differing also in macroscopic characteristics (i.e. gel or powder NCC), were developed and evaluated. Beside NCC, hydrogels also consisted of one of three different natural polymers (alginate, pectin or low viscosity chitosan), glycerol, and betamethasone dipropionate (BDP) as model active pharmaceutical intgredient (API) otherwise used to treat AD. We first focused on optimizing the incorporation of BDP in the form of a self-microemulsifying system (SMES) into hydrogels. The differential scanning calorimetry (DSC) method confirmed that the API incorporated in the hydrogels was dissolved. The influence of two different NCC and SMES on the viscosity and amplitude and frequency dependence of the elastic and plastic modulus was evaluated by rheological measurements. The powderish NCC was found to form more viscous hydrogels while the addition of SMES (with or without incorporated BDP) either increased or decreased the viscosity or the values of one or both modules, depending on the natural polymer and NCC used. Furthermore, films were prepared from hydrogels containing SMES (with and without BDP) using the solvent evaporation method. The prepared films showed a low residual moisture content (up to 2,15 % m/m) and a maximum thickness of 0,090 ± 0,007 mm. In addition, the prepared films showed a statistically significant difference in water retention ability after application to a cellulose acetate membrane. The hydrogels produced have proven to be potential delivery systems for BDP in the treatment of AD.

Keywords:atopic dermatitis, hydrogels, xerogels, nanocrystalline cellulose, betamethasone dipropionate

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