Alginate hydrogels are widely used in wound dressings due to hydrophilicity, biocompatibility,
flexibility, and high sorption capacity, providing effective moisture regulation in wounds and inducing
rapid granulation and reepithelization of the damaged tissue. However, these dressings are not
bioactive so that different methodologies have been investigated to extend functionality of alginate
hydrogels.
In the present work, we show several approaches to achieve this aim by addition of different
biologically active components. These include incorporation of silver nanoparticles as potent
antimicrobial agents (1), bioactive honey components (2), activated charcoal (AC) particles as carriers
of therapeutically active agents (3) as well as the use of Zn-alginate hydrogels that release zinc ions (4).
The obtained composites were comprehensively characterized regarding composition, cytotoxicity,
antibacterial activity, release kinetics of active agents and wound treatment in a rat model.
Ag/alginate nanocomposite hydrogels releasing silver ions and/or nanoparticles exhibited high
bactericidal activity against a broad spectrum of standard and multi-drug resistant clinical bacterial
strains (Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus – MRSA,
Acinetobacter baumannii and Pseudomonas aeruginosa). Especially interesting results were obtained
against 13 clinical isolates of A. baumannii, which were completely extinguished over 48 h in 6 cases
(2). However, in 3 clinical isolates, antibacterial effects were not noticed implying possibility for
development of bacterial resistance to silver. In the treatment of 2nd degree burns in rats Ag/alginate
nanocomposites exhibited the same efficiency as commercial medical products (5).
Composite alginate hydrogels with immobilized AC particles impregnated with povidone iodine
(PVP-I) as a model therapeutically active agent, were developed with the aim to provide controlled
particle release in the wound without actually releasing the adsorbed substance, thus achieving the
desired activity without adverse effects by systemic absorption. The composite Ca-alginate hydrogels
induced strong bactericidal effects against two standard bacterial strains and clinical multi-resistant
wound isolates (MRSA, E. coli, P. aeruginosa, Еnterococcus faecalis and Proteus mirabilis) without
releasing PVP-I in the environment (3). Furthermore, composite Zn-alginate hydrogels released zinc
ions in addition to AC particles with adsorbed PVP-I, which induced additional microbicidal effects on
one wild yeast strain (Candida albicans). The obtained bactericidal effects were ascribed to effective
adsorption of bacteria onto AC particles and further direct contact with the adsorbed iodine, while the
antifungal activity against C. albicans was assigned to released Zn 2+.
Overall, the developed composite alginate hydrogels have shown high potentials for utilization
in variety of multifunctional wound dressings according to the specific needs.Alginatni hidrogelovi se široko koriste u oblogama za rane zbog svoje hidrofilnosti,
biokompatibilnosti, fleksibilnosti i velikog sorpcionog kapaciteta čime obezbeđuju efikasnu regulaciju
vlažnosti rane i podstiču brzu granulaciju i reepitelizaciju oštećenog tkiva. Međutim, ove obloge nisu
bioaktivne tako da su istraživane različite metodologije kako bi se proširila funkcionalnost alginatnih
hidrogelova.
U ovom radu je prikazano nekoliko pristupa ostvarivanju tog cilja dodatkom različitih biološki
aktivnih komponenata. Ovi pristupi uključuju inkorporaciju nanočestica srebra kao potentnog
antimikrobnog agensa (1), bioaktivnih komponenata meda (2), čestica aktivnog uglja (AU) kao nosača
terapeutski aktivnih agenasa (3), kao i primenu hidrogelova Zn-alginata koji otpuštaju jone cinka.
Dobijeni kompoziti su sveobuhvatno karakterisani u pogledu sastava, citotoksičnosti, antibakterijske
aktivnosti, kinetike otpuštanja aktivnih agenasa i tretmana rana u eksperimentalnom modelu
opekotina na pacovima.
Ag/alginatni nanokompozitni hydrogelovi su usled otpuštanja jona i/ili nanočestica srebra,
pokazali izraženu baktericidnu aktivnost prema širokom spektru standardnih i kliničkih multi-
rezistentnih bakterijskih sojeva (Escherichia coli, Staphylococcus aureus, meticilin-resistentni
Staphylococcus aureus – MRSA, Acinetobacter baumannii i Pseudomonas aeruginosa). Posebno
interesantni rezultati su dobijeni u kulturama 13 kliničkih izolata A. baumannii, gde je u 6 slučajeva
postignut potpun baktericidan efekat u toku 48 h (2). Ipak, kod 3 klinička izolata nije postignuto
antibakterijsko dejstvo što ukazuje na mogućnost razvoja bakterijske rezistencije na srebro. U
tretmanu opekotina drugog stepena na pacovima, Ag/alginatni nanokompoziti su pokazali istu
efikasnost kao komercijalni medicinski proizvodi.
Kompozitni alginatni hidrogelovi sa imobilisanim česticama AU impregniranih povidon-jodom
kao model terapeutski aktivnom komponentom, su razvijeni sa ciljem da obezbede kontrolisano
otpuštanje čestica AU u rani bez otpuštanja adsorbovane supstance kako bi se na taj način postiglo
željeno dejstvo bez neželjenih efekata sistemske apsorpcije. Kompozitni Ca-alginatni hidrogelovi su
pokazali jake baktericidne efekte na dva standardna bakterijska soja i nekoliko kliničkih multi-
rezistentnih izolata iz rana (MRSA, E. coli, P. aeruginosa, Еnterococcus faecalis i Proteus mirabilis) bez
otpuštanja povidon-joda u okolinu (3). Isto tako, kompozitni Zn-alginatni hidrogelovi su otpuštali jone
cinka uz otpuštanje AU čestica sa adsorbovanim povidon-jodom što je prouzrokovalo dodatno
mikrobicidno dejstvo na jedan divlji soj gljivice Candida albicans. Dobijeni baktericidni efekti su
pripisani efikasnoj adsorpciji bakterija na čestice AU i daljem direktnom kontaktu adsorbovanog joda
sa ćelijskom membranom bakterija, dok je antifungalna aktivnost u odnosu na C. albicans pripisana
otpuštenim Zn 2+ jonima.
Može se zaključiti da su razvijeni kompozitni alginatni hdrogelovi pokazali veliki potencijal za
primenu u raznovrsnim multifunkcionalnim oblogama za rane prilagođenim specifičnim potrebama.Drugi naučni simpozijum Saveza farmaceutskih udruženja Srbije sa međunarodnim učešćem, 28. 10. 2021. Beogra
