| Abstract | Cilj istraživanja:
Cilj ovog rada bio je prikupiti znanstvena saznanja i prezentirati sustavni pregled o mogućnostima topikalne
primjene različitih formulacija resveratrola s objektivnim i kritičkim osvrtom na provedena in vitro istraživanja
na staničnim kulturama i in vivo istraživanja na animalnim modelima te eventualnim kliničkim studijama na
ljudima. Također, cilj ovog rada je bio na temelju prikupljenih podataka odgovoriti na slijedeća pitanja:
1. Što možemo očekivati od molekule resveratrola: budući „multitarget“ lijek, dodatak prehrani za
prevenciju bolesti ili oboje?
2. Na koji način se mogu poboljšati loša farmakokinetička svojstva grožđanih polifenola, posebno
resveratrola?
3. Može li topikalna primjena nanoformulacija resveratrola riješiti sve probleme farmakokinetike
resveratrola?
Materijali i metode:
Ciljana literaturna pretraga je provedena korištenjem konstruktivnih sintaksi na certificiranim i akreditiranim
bazama podataka npr. Pubmed (Medline), Elsevier ScienceDirect, Scopus, Evolve, Knovel, Reaxys, ClinicalKey,
Allied and Complementary Medicine Database, Natural Medicine Comprenhensive Database, Embase i
Cochrane Library, Human Metabolome Database, Kyoto Encyclopedia of Genes and Genomes te ISI Web of
Knowledge Science Citation Index Expanded i Phenol Explorer 2.0. Phenol Explorer je opsežna javno dostupna
baza podataka pokrenuta 2009. godine čiji se podaci periodički ažuriraju. Literaturni pregled obuhvaća razdoblje
do kolovoza 2016. i oslanja se na javnodostupne baze.
Rezultati:
Bioraspoloživost topikalno primijenjenog resveratrola se može povećati primjenom poboljšivača permeacije u
sustavu mikroemulzija i polimernih otopina, sintezom i/ili evaluacijom prolijekova resveratrola i konjugiranih
metabolita resveratrola, kombiniranjem resveratrola s in vivo inhibitorima metabolizma resveratrola te
primjenom nanotehnologije.
Najčešće nanočestice koje osiguravaju ciljanu dostavu resveratrola za oralnu i topikalnu primjenu su lipidne
nanočestice (liposomi, etosomi, propilenglikol liposomi, niosomi, transferosomi, transetosomi, fitosomi, čvrste
lipidne nanočestice i nanostrukturirani lipidni nosači te nanoemulzije) i polimerne nanočestice (ciklodekstrini,
kuglice kalcijeva i cinkova pektinata, kitozanske nanočestice, nanočestice PLGA i PEG, nanosfere, nanokapsule,
dendrimeri i polimerne micele).
Zaključak:
Loša farmakokinetička svojstva resveratrola se mogu poboljšati topikalnom primjenom nanočestica resveratrola
te oralnom i topikalnom primjenom nanokapsula resveratrola koje sadrže kvercetin ili piperin kao inhibitore
metabolizma resveratrola. Na temelju provedenih istraživanja, resveratrol se koristi kao adjuvantni
kemoterapeutik jer posjeduje sinergistički učinak s kemoterapeuticima poput doksorubicina čime osigurava
smanjenje potrebne doze i rizika od fatalnih nuspojava. Kako bi se u potpunosti iskoristio izuzetni farmakološki
potencijal resveratrola kao standardnog kliničkog terapeutika, potrebno je provesti dugotrajne epidemiološke
studije i kontrolirana klinička istraživanja s velikim brojem volontera. |
| Abstract (english) | Objectives:
The aim of this study was to collect scientific knowledge and to present a systematic review of the possibilities
of topical application of various formulations of resveratrol with objective and critical review of the research
conducted in vitro on cell cultures and in vivo studies in animal models and eventual clinical trials in humans.
Also, the aim of this study was based on data collected to answer the following questions:
1. What can we expect from a molecule of resveratrol: since ˝multitarget˝ drug, dietary supplement for the
prevention of disease, or both?
2. How can improve poor pharmacokinetic properties of grape polyphenols, especially resveratrol?
3. Can topical application of resveratrol nanoformulations solve all the problems pharmacokinetics of
resveratrol?
Materials and methods:
Targeted literature search was conducted using structural syntax to certified and accredited databases eg,
PubMed (Medline), Elsevier ScienceDirect, Scopus, Evolve, Knovel, Reaxys, ClinicalKey, Allied and
Complementary Medicine Database, Natural Medicine Comprenhensive Database, Embase and the Cochrane
Library, Human Metabolome Database, the Kyoto Encyclopedia of Genes and Genomes, and ISI Web of
Knowledge Science Citation Index Expanded and Phenol Explorer 2.0. Phenol Explorer is a comprehensive
public database launched in 2009, whose data is periodically updated. The literature review covers the period up
to August 2016.
Results:
The bioavailability of topically applied resveratrol can be increased using the permeation enhancers in the
microemulsion system and polymer solutions, synthesis and/or evaluation of prodrugs of resveratrol and
conjugated metabolites of resveratrol, combining resveratrol with in vivo inhibitors of metabolism of resveratrol
and the application of nanotechnology.
The most common nanoparticles to provide for targeted delivery of resveratrol for oral and topical administration
are the lipid nanoparticles (liposomes, ethosomes, propylene glycol liposomes, niosomes, transferosomes,
transetosomes, phytosomes, solid lipid nanoparticles and nanostructured lipid carriers and nanoemulsions) and
polymeric nanoparticles (cyclodextrins, beads of calcium and zinc pectinate, chitosan nanoparticles,
nanoparticles of PLGA and PEG, nanospheres, nanocapsules, micelles and dendrimers).
Conclusion:
Poor pharmacokinetic properties of resveratrol can be improved by topical application of nanoparticles and oral
resveratrol and resveratrol topical application of nanocapsules containing piperine, quercetin, or as inhibitors of
the metabolism of resveratrol. Based on the research, resveratrol is used as adjuvant chemotherapy because it has
a synergistic effect with chemotherapeutic agents such as doxorubicin, which ensures reduction in the required
dose and risk of fatal side effects. In order to fully utilize the exceptional pharmacological potential of
resveratrol as a standard clinical therapeutics, it is necessary to conduct long-term epidemiological studies and
controlled clinical trials with a large number of volunteers. |
