Title
Composite reservoirs with crosslinked poly(acrylic acid) hydrogel for controlled drug delivery via nonspecific electrical interactions: doctoral dissertation
Creator
Janićijević, Željko, 1988-, 62096393
Copyright date
2020
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Autorstvo-Nekomercijalno-Deliti pod istim uslovima 3.0 Srbija (CC BY-NC-SA 3.0)
License description
Dozvoljavate umnožavanje, distribuciju i javno saopštavanje dela, i prerade, ako se navede ime autora na način odredjen od strane autora ili davaoca licence i ako se prerada distribuira pod istom ili sličnom licencom. Ova licenca ne dozvoljava komercijalnu upotrebu dela i prerada. Osnovni opis Licence: http://creativecommons.org/licenses/by-nc-sa/3.0/rs/deed.sr_LATN Sadržaj ugovora u celini: http://creativecommons.org/licenses/by-nc-sa/3.0/rs/legalcode.sr-Latn
Language
English
Cobiss-ID
Theses Type
Doktorska disertacija
description
Datum odbrane: 14.10.2020.
Other responsibilities
mentor
Vujisić, Miloš, 1974-, 13838439
član komisije
Ciraj-Bjelac, Olivera, 1972-, 1787751
član komisije
Obradović, Bojana, 1966-, 12722535
član komisije
Stevanović, Magdalena, 1974-, 62304265
član komisije
Mihailović, Peđa, 1973-, 25418599
University
Univerzitet u Beogradu
Faculty
Elektrotehnički fakultet
Alternative title
Kompozitni rezervoari sa umreženim hidrogelom poli(akrilne kiseline) za kontrolisanu dostavu lekova putem nespecifičnih električnih interakcija
Publisher
[Ž.Janićijević]
Format
XI, 102 str.
description
Biomaterials Engineering - Biomaterials for Drug Delivery
Abstract (en)
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.
Abstract (sr)
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.
Authors Key words
composite hydrogel, liquid phase inversion, drug reservoirs, cationic drugs, ion exchange,
diffusion, iontophoresis, drug release
Authors Key words
kompozitni hidrogel, mokra fazna inverzija, rezervoari za lekove, katjonski lekovi, jonska
izmena, difuzija, jontoforeza, otpuštanje leka
Classification
621.039.8:544.773.432:615.015.3(043.3)
Type
Tekst
Abstract (en)
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.
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