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Composite reservoirs with crosslinked poly(acrylic acid) hydrogel for controlled drug delivery via nonspecific electrical interactions

Kompozitni rezervoari sa umreženim hidrogelom poli(akrilne kiseline) za kontrolisanu dostavu lekova putem nespecifičnih električnih interakcija

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Disertacija.pdf (7.140Mb)
IzvestajKomisije23504.pdf (1.562Mb)
Author
Janićijević, Željko
Mentor
Vujisić, Miloš
Committee members
Ciraj-Bjelac, Olivera
Obradović, Bojana
Stevanović, Magdalena
Mihailović, Peđa
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Abstract
Transdermal and subcutaneous drug delivery routes offer many advantages compared to the enteral route of drug administration including improved drug bioavailability, maintenance of optimal drug levels in the systemic circulation, reduction of toxicity, and better patient compliance. The overall aim of this dissertation was to synthesize and characterize composite hydrogels composed of the cross-linked poly(acrylic acid) hydrogel and the hydrophobic polymer base that are suitable for the storage and controlled delivery of cationic drugs mediated by non-specific electrical interactions. We successfully synthesized composite hydrogel membranes and implants by combining the ultraviolet or gamma irradiation-induced polymerization and liquid phase inversion. Physicochemical properties of the materials, such as chemical composition, microstructure, ion-exchange capacity, swelling behavior, and ionic conductivity, were analyzed. In vitro release from composite hydrogel reservoirs was ...investigated using methylene blue as the model drug. Examined composite hydrogel reservoirs showed mainly diffusion-controlled release kinetics. We developed a modeling approach based on the analytical solution for diffusion and the empirical Weber-Morris model that effectively describes the release kinetics using the concept of apparent diffusion coefficient. Rate-limiting barriers defined by the composite hydrogel microstructure and ion exchange governed the passive release kinetics. Iontophoretic excitation of composite membranes confirmed their electrical responsivity and induced an effective increase in the apparent diffusion coefficient. Obtained composite hydrogels hold promise for drug delivery, but also for applications in nanomaterial synthesis and iontronics.

Transdermalni i subkutani načini dostave aktivnih supstanci nude brojne prednosti u poređenju sa enteralnim načinom jer se postiže veća bioraspoloživost leka, njegova optimalna koncentracija u sistemskoj cirkulaciji, smanjena toksičnost i veća komfornost pacijenata. Glavni cilj ove disertacije bila je sinteza i karakterizacija kompozitnih hidrogelova koji sadrže umreženi hidrogel poli(akrilne kiseline) i hidrofobnu polimernu bazu, a pogodni su za skladištenje i kontrolisanu dostavu katjonskih lekova putem nespecifičnih električnih interakcija. Kompozitni hidrogelovi, u formi membrana i implantata, su uspešno sintetisani kombinovanjem metoda polimerizacije indukovane ultraljubičastim ili gama zračenjem i metode mokre fazne inverzije. Analizirana su fizičko-hemijska svojstva materijala kao što su hemijski sastav, mikrostruktura, jonoizmenjivački kapacitet, karakteristike bubrenja i jonska provodljivost. Proces otpuštanja aktivne supstance iz kompozitnih rezervoara sa hidrogelom ...je ispitivan u in vitro uslovima korišćenjem metilenskog plavog kao model leka. Ispitani kompozitni rezervoari sa hidrogelom su pokazali uglavnom difuziono kontrolisanu kinetiku otpuštanja. Razvijen je pristup modelovanju zasnovan na analitičkom rešenju za difuziju i empirijskom Veber-Moris modelu koji efektivno opisuje kinetiku otpuštanja korišćenjem koncepta prividnog koeficijenta difuzije. Kinetika pasivnog otpuštanja je bila diktirana barijerama definisanim mikrostrukturom kompozitnog hidrogela i jonskom izmenom. Jontoforetska pobuda kompozitnih membrana potvrdila je njihovu elektroresponzivnost i indukovala efektivni porast prividnog koeficijenta difuzije. Očekuje se da dobijeni kompozitni hidrogelovi pronađu primenu u dostavi lekova, kao i u sintezi nanomaterijala i jontronici.

Faculty:
University of Belgrade, School of Electrical Engineering
Date:
14-10-2020
Keywords:
composite hydrogel, liquid phase inversion, drug reservoirs, cationic drugs, ion exchange, diffusion, iontophoresis, drug release / kompozitni hidrogel, mokra fazna inverzija, rezervoari za lekove, katjonski lekovi, jonska izmena, difuzija, jontoforeza, otpuštanje leka
[ Google Scholar ]
URI
http://eteze.bg.ac.rs/application/showtheses?thesesId=7803
https://fedorabg.bg.ac.rs/fedora/get/o:23060/bdef:Content/download
http://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=28206345
https://nardus.mpn.gov.rs/handle/123456789/17707

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