Uticaj farmaceutsko-tehnološke formulacije u obliku mikrovezikula sa alginatom na resorpciju gliklazida iz digestivnog trakta pacova / The effect of alginate microcapsules pharmaceutical formulation on gliclazide absorption in rat gastrointestinal tract

Description

<p>Gliklazid je jedan od najče&scaron;će kori&scaron;ćenih lekova u terapiji dijabetes melitusa tip 2. U poslednje vreme, utvrđeno je da gliklazid ispoljava i druge pozitivne farmakolo&scaron;ke efekte kao &scaron;to su imunomodulatorni i anti-koagulacioni efekti, ukazujući na njegovu potencijalnu primenu u terapiji dijabetes melitusa tip 1. Gliklazid se odlikuje varijabilnim stepenom apsorpcije nakon peroralne primene i iz tog razloga pretpostavlja se da bi tehnike njegove ciljane isporuke, kao &scaron;to je mikroinkapsulacija, mogle da dovedu do pobolj&scaron;anja njegove apsorpcije i njegove potencijalne primene u terapiji T1DM. Pokazano je da različite žučne kiseline, uključujući i holnu, imaju stabilizacione efekte u domenu primene mikrovezikula i kontrolisanog osobađanja lekova, te je moguće da bi njihov dodatak u mikrovezikularnu formulaciju gliklazida mogao dodatno da pobolj&scaron;a oslobađanje gliklazida, njegovu apsorpciju i antidijabetičke efekte. S tim u vezi, cilj ovog istraživanja je da se ispita hipoglikemijski efekat gliklazida primenjenog u obliku alginatnih mikrovezikula, sa ili bez dodatka holne kiseline na T1DM modelu pacova. Trideset &scaron;est pacova obolelih od T1DM indukovanog aloksanom i odgovarajuće zdrave kontrolne životinje su nasumično raspoređene u &scaron;est grupa (n=6) i tretirane jednokratnom dozom fiziolo&scaron;kog rastvora, suspenzijom gliklazida, gliklazidom u obliku alginatnih mikrovezikula, samo holnom kiselinom, i mikrovezikulama gliklazida sa ili baz dodatka holne kiseline. Uzorkovana je krv tokom 10 h nakon unete doze i merena je koncentracija glukoze u krvi I koncentracija gliklazida u serumu kori&scaron;ćenjem HPLC metode. Mikrovezikule gliklazida su ispoljile hipo-glikemijski efekat kod pacova obolelih od dijabetesa, uprkos njegovim smanjenim koncentracijama u serumu, dok je dodatak holne kiseline u mikrovezikularnu formulaciju smanjio hipoglikemijski efekat gliklazida. Ovo potvrđuje izostanak sinergističkog efekta između gliklazida i holne kiseline. Takođe, ni proces mikroinkapsulacije niti dodatak holne kiseline nisu doprineli pobolj&scaron;anju apsorpcije gliklazida, &scaron;to ukazuje na činjenicu da su njegovi hipoglikemijski efekti nezavisni od njegove apsorpcije i koncentracije u serumu. Stoga se može pretpostaviti da su hipoglikemijski efekti gliklazida pre pod uticajem crevno-metaboličke aktivacije nego ciljanog oslobađanja u digestivnom traktu sistemske apsorpcije. Mikrovezikule gliklazida ispoljavaju hipoglikemijski efekat kod pacova obolelih od T1DM nezavisno od insulina, te mogu imati potencijalnu primenu u terapiji T1DM. Ovaj rad su podržali: HORIZON 2020 MEDLEM projekat broj 690876; Projekat Sekretarijata naučnog i tehnolo&scaron;kog razvoja Vojvodine broj . 114-451-2072-/2016-02; Projekat Ministarstva obrazovanja, nauke i tehnolo&scaron;kog razvoja Republike Srbije broja 41012.</p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>mladen</o:Author> <o:Version>16.00</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-US</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> 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1. https://www.cris.uns.ac.rs/DownloadFileServlet/Disertacija154564049440531.pdf?controlNumber=(BISIS)110023&fileName=154564049440531.pdf&id=12451&source=NDLTD&language=en
2. https://www.cris.uns.ac.rs/record.jsf?recordId=110023&source=NDLTD&language=en

Tags

Additional Fields

Identifer	oai:union.ndltd.org:uns.ac.rs/oai:CRISUNS:(BISIS)110023
Date	24 April 2019
Creators	Ćalasan Jelena
Contributors	Goločorbin-Kon Svetlana, Vasović Velibor, Milijašević Boris, Vukmirović Saša, Atanacković Krstonošić Milica, Dobrić Silva
Publisher	Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, University of Novi Sad, Faculty of Medicine at Novi Sad
Source Sets	University of Novi Sad
Language	Serbian
Detected Language	Unknown
Type	PhD thesis