Design and characterization of antibacterial electrospun drug delivery systems for wound infections
Kuupäev
2022-01-17
Autorid
Ajakirja pealkiri
Ajakirja ISSN
Köite pealkiri
Kirjastaja
Abstrakt
Halvasti paranevad haavad on kaasaegses ühiskonnas kiiresti kasvav sotsiaalmajanduslik probleem. Haavapatoloogiate kujunemises mängivad rolli mitmed faktorid, kuid järjest suuremat tähtsust selles omistatakse biofilmile ja mikrobioloogilise tasakaalu häirumisele haavakeskkonnas. Kaasaegsed haavakatted, kuhu on võimalik viia antimikroobseid raviaineid (RA) ning kontrollida nende vabanemiskineetikat, saavutamaks lokaalseid kliiniliselt olulisi RA kontsentratsioone pikema aja vältel, võivad oluliselt parandada ravikvaliteeti. Elektrospinnimine (ES) on lihtne ja paindlik meetod polümeersete nano- ja mikrofiibermaatriksite valmistamiseks, võimaldades lisada erinevaid RA-sid ning kontrollida nende vabanemist. Lisaks on fiibermaatriksitel mitmeid struktuurseid omadusi, mis teevad neist perspektiivikad haavakattematerjalid. Siiski on endiselt palju teadmata erinevate disainiaspektide mõjust ES-tud fiibermaatriksite funktsionaalsusele ja kvaliteedile. Käesolevas töös valmistati ES teel erinevate omadustega nano- ja mikrofiibermaatrikseid, kasutades erinevaid kandjapolümeere ja antibakteriaalseid RA-sid. ES mõjutas RA tahket vormi ning polümeeride kristallilisust, samuti kutsus esile interaktsioone erinevate maatriksi komponentide vahel. Erinevad fiibermaatriksid vabastasid RA-d erinevalt, kusjuures üheks olulisemaks, aga mitte universaalseks, faktoriks osutus nende märgumine ja puhverlahuse tungimine maatriksisse. Uudsed hüdrogeelidel põhinevad analüüsimeetodid RA vabanemise ja difusiooni hindamiseks jäljendasid võrreldes puhverlahustega paremini in vitro antibakteriaalse aktiivsuse testimise ja arvatavasti ka haavakeskkonna tingimusi. Difusioonitesti abil agarsöötmes sai hinnata vabanenud RAde efektiivsust erinevate mikroorganismide suhtes. Uudsete meetoditega sai lisaks tuvastada erinevusi erineva RA vabanemisprofiiliga maatriksite antibakteriaalses aktiivsuses. Selgus, et aeglane RA vabanemine aitab takistada fiibermaatriksile biofilmi moodustumist, ning et ilma RA-ta haavakate võib olla soodne pind biofilmi tekkeks. Fiibermaatrikseid oli võimalik erinevatel viisidel efektiivselt steriliseerida, kuid see protsess võis muuta maatriksi omadusi sõltuvalt konkreetsest steriliseerimismeetodist ja maatriksi materjalidest.
Nonhealing wounds represent an escalating socioeconomic problem in modern society. Several factors contribute to the wound pathologies, but it is increasingly recognized that biofilm and microbial unbalance that overwhelms hosts’ immune responses play a major part in it. Advanced wound dressings that have the capability to deliver antimicrobial drugs to the site of action at controlled rate for extended period, establishing localized, clinically relevant drug concentrations, can potentially improve therapeutic outcomes. Electrospinning (ES) is a simple and flexible method to produce polymeric nano- and microfiber matrices, enabling to incorporate different drugs and control their release. In addition, fiber matrices have several structural properties that make them promising wound dressing materials. Still, much is unknown about different aspects of the design on the performance and quality of these matrices. In the present thesis, ES was used to produce different nano- and microfiber matrices, using different carrier polymers and antibacterial drugs. ES affected the solid-state form of the drug and polymer crystallinity, also induced interactions between different components of the matrix. Different matrices released the drug differently. One of the most important, although not universal, factors controlling drug release was the wetting and buffer penetration into the matrix. Novel hydrogel-based methods to study drug release and diffusion appeared to mimic the in vitro antibacterial activity testing conditions and probably wound environment better compared to the release into buffer solution. Traditional disc diffusion tests enabled to evaluate the efficacy of released drugs against different microorganisms, whereas novel methods helped to reveal differences in the antibacterial activity of differently designed electrospun fiber matrices. It was shown that prolonged release of the drug helped to prevent biofilm formation on the fiber matrix, whereas some carrier polymers could promote biofilm formation on matrices without the drug. Different sterilization methods can effectively sterilize fiber matrices, although this could change the matrix properties, depending on the process conditions and matrix materials.
Nonhealing wounds represent an escalating socioeconomic problem in modern society. Several factors contribute to the wound pathologies, but it is increasingly recognized that biofilm and microbial unbalance that overwhelms hosts’ immune responses play a major part in it. Advanced wound dressings that have the capability to deliver antimicrobial drugs to the site of action at controlled rate for extended period, establishing localized, clinically relevant drug concentrations, can potentially improve therapeutic outcomes. Electrospinning (ES) is a simple and flexible method to produce polymeric nano- and microfiber matrices, enabling to incorporate different drugs and control their release. In addition, fiber matrices have several structural properties that make them promising wound dressing materials. Still, much is unknown about different aspects of the design on the performance and quality of these matrices. In the present thesis, ES was used to produce different nano- and microfiber matrices, using different carrier polymers and antibacterial drugs. ES affected the solid-state form of the drug and polymer crystallinity, also induced interactions between different components of the matrix. Different matrices released the drug differently. One of the most important, although not universal, factors controlling drug release was the wetting and buffer penetration into the matrix. Novel hydrogel-based methods to study drug release and diffusion appeared to mimic the in vitro antibacterial activity testing conditions and probably wound environment better compared to the release into buffer solution. Traditional disc diffusion tests enabled to evaluate the efficacy of released drugs against different microorganisms, whereas novel methods helped to reveal differences in the antibacterial activity of differently designed electrospun fiber matrices. It was shown that prolonged release of the drug helped to prevent biofilm formation on the fiber matrix, whereas some carrier polymers could promote biofilm formation on matrices without the drug. Different sterilization methods can effectively sterilize fiber matrices, although this could change the matrix properties, depending on the process conditions and matrix materials.
Kirjeldus
Väitekirja elektrooniline versioon ei sisalda publikatsioone
Märksõnad
wound treatment, drug carriers, nanofibers, disinfection, antimicrobial effect