Priprava, karakterizacija in aplikacija polisaharidnih aerogelov

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 bodytherefore, the need for intravenous, post-operational treatment is greatly reduced.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

A Brief Evaluation of Pore Structure Determination for Bioaerogels

This review discusses the most commonly employed methods for determining pore size and pore size distribution in bioaerogels. Aerogels are materials with high porosity and large surface areas. Most of their pores are in the range of mesopores, between 2 and 50 nm. They often have smaller or larger pores, which presents a significant challenge in determining the exact mean pore size and pore size distribution in such materials. The precision and actual value of the pore size are of considerable importance since pore size and pore size distribution are among the main properties of aerogels and are often directly connected with the final application of those materials. However, many recently published papers discuss or present pore size as one of the essential achievements despite the misinterpretation or the wrong assignments of pore size determination. This review will help future research and publications evaluate the pore size of aerogels more precisely and discuss it correctly. The study covers methods such as gas adsorption, from which BJH and DFT models are often used, SEM, mercury porosimetry, and thermoporometry. The methods are described, and the results obtained are discussed. The following paper shows that there is still no precise method for determining pore size distribution or mean pore size in aerogels until now. Knowing that, it is expected that this field will evolve in the future

Simple, One-Pot Method for Preparing Transparent Ethyl Cellulose Films with Good Mechanical Properties

In this research, ethyl cellulose films were prepared by a simple, easy, controlled one-pot method using either ethanol or ethyl lactate as solvents, the films being formed at 6 °C. Titanium dioxide nanoparticles were incorporated to improve the oxygen transmission and water vapour transmission rates of the obtained films. This method used no plasticizers, and flexible materials with good mechanical properties were obtained. The resulting solvent-free and transparent ethyl cellulose films exhibited good mechanical properties and unique free-shapable properties. The obtained materials had similar properties to those reported in the literature, where plasticizers were incorporated into ethyl cellulose films with an elastic modulus of 528 MPa. Contact angles showed the hydrophobic nature of all the prepared materials, with contact angles between 80 and 108°. Micrographs showed the smooth surfaces of the prepared samples and porous intersections with honeycomb-like structures. The oxygen and water vapor transmission rates were the lowest for the ethyl cellulose films prepared in ethyl lactate, these being 615 cm3·m−2·day−1 and 7.8 gm−2·day−1, respectively, showing that the films have promise for food packaging applications

Hybrid Polylactic-Acid–Pectin Aerogels: Synthesis, Structural Properties, and Drug Release

Wound-dressing materials often include other materials stimulating wound healing. This research describes the first formulation of biodegradable hybrid aerogels composed of polylactic acid and pectin. The prepared hybrid material showed a highly porous structure with a surface area of 166 ± 22.6 m2·g−1. The addition of polylactic acid may have decreased the surface area of the pure pectin aerogel, but it improved the stability of the material in simulated body fluid (SBF). The pure pectin aerogel showed a high swelling and degradation ratio after 3 h. The addition of the polylactic acid prolonged its stability in the simulated body fluid from 24 h to more than one week, depending on the amount of polylactic acid. Biodegradable aerogels were loaded with indomethacin and diclofenac sodium as model drugs. The entrapment efficiencies were 63.4% and 62.6% for indomethacin and diclofenac sodium, respectively. Dissolution of both drugs was prolonged up to 2 days. Finally, sodium percarbonate and calcium peroxide were incorporated into the bioaerogels as chemical oxygen sources, to evaluate oxygen generation for potential wound healing applications