Ispitivanje vezanja biološki aktivnih tvari za humani serumski albumin HPLC tehnikom

master's thesis

• Title (english): The assay of binding biologically active supstances to human serum albumin using HPLC
• Author: Sandra Mak
• Mentor: Miranda Sertić (mentor)
• Committee member: Miranda Sertić (predsjednik povjerenstva)
• Committee member: Ana Mornar Turk (član povjerenstva)
• Committee member: Olga Gornik (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2016-09-28, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Vezanje lijeka za proteine u plazmi je neizbježan proces nakon što je lijek distribuiran u krvotok te utječe na farmakokinetičke i farmakodinamičke parametre lijekova. Pošto mijenja dostupnost lijeka za mjesto djelovanja i udio slobodnog/nevezanog lijeka koji je odgovoran za biološki učinak, vezanje za proteine plazme je ključno za procjenu jačine i duljine terapeutskog djelovanja lijeka i u dizajnu optimalnog režima doziranja.
Fitoestrogeni su prirodni biljni spojevi nestereoidne strukture koji su funkcionalno ili strukturno slični estrogenima te se mogu vezati na endogene estrogene receptore. Zbog potencijalno pozitivnih i negativnih bioloških učinaka na organizam važno je odrediti njihovu bioraspoloživost odnosno udio slobodnih/nevezanih fitoestrogena koji može imati farmakološki učinak. U ovom diplomskom radu ispitano je vezanje fitoestrogena za humani serumski albumin tekućinskom kromatografijom visoke djelotvornosti s kromatografskom kolonom Chiralpak HSA.
U ispitivanju su fitoestrogeni pokazali visok postotak vezanja za humani serumski albumin (79-95%) što znači da je mali udio slobodnih fitoestrogena dostupan za biološki učinak. Primijećeno je da male razlike u supstituentima, poput metiliranja hidroksilne skupine ili prisutnost glikozidne skupine, imaju odraz na vrijednosti vezanja za humani serumski albumin odnosno na vrijeme retencije i postotak vezanja za HSA. Stoga modifikacijom strukture fitoestrogena možemo utjecati na njihovu distribuciju i učinak u organizmu.

Abstract (english)

Drug binding to plasma proteins is an inevitable process after the drug is distributed in the blood stream and it affects the pharmacokinetic and pharmacodynamic parameters of drugs. Since it changes the availability of the drug for the site of action and the free/unbounded fraction which is responsible for the biological effect, binding to plasma proteins is essential for the assessment of the strength and length of therapeutic action of drugs and in design of optimal dosage regimens.
Phytoestrogens are natural plant compounds with non-steroidal structures which are functionally and structurally similar to estrogen and can bind to endogenous estrogen receptors. Due to the potentially positive and negative biological effects on the body, it is important to determine their bioavailability and proportion free/unbound fractions of phytoestrogens which can have a pharmacological effect. In this thesis binding of phytoestrogens to human serum albumin was examined by high performance liquid chromatography with chromatography column Chiralpak HSA.
The assay showed high percentage of binding of phytoestrogens to human serum albumin (79-95%), which means that small fractions of phytoestrogens are free and available for biological effect. It was observed that small variations in substituents, such as methylation of the hydroxyl group or the presence of a glycoside, reflect on the binding to human serum albumin, or the retention time and the percentage of binding to HSA. Therefore, modifying the structure of phytoestrogens can affect their distribution and effect on the body.

• Keywords: vezanje za proteine plazme; humani serumski albumin; HSA kolona; fitoestrogeni; kromatografija
• Keywords (english): drug binding to plasma proteins; human serum albumin; HSA column; phytoestrogens; chromatography
• Language: croatian
• URN:NBN: urn:nbn:hr:163:833468
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-09-13 12:11:35