Naslov
Microfluidic Enzyme Reactor with Immobilized Human Intestinal Microsomes

Autori
Duvnjak, Zrinka

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad, diplomski

Fakultet
Farmaceutsko-biokemijski fakultet

Mjesto
Zagreb

Datum
07.04

Godina
2022

Stranica
58

Mentor
Sikanen, Tiina ; Rimac, Hrvoje

Ključne riječi
IMER, microfluidics, immobilization, intestinal metabolism, CYP1B1

Sažetak
Human intestinal metabolism is emerging to be more important than what was previously thought, especially in pharma industry when the inhibitory potential of a new drug candidate is being determined. It was shown that intestinal metabolism has a critical role in determining a need for clinical drug-drug interaction studies for weak CYP3A perpetrators. On the other hand, conventional static in vitro enzymatic assays demand a high consumption of enzymes and other chemicals, the separation step is always needed before product detection, and without flow-through conditions, there are limitations in imitating conditions in human body. In this work, the first in its kind immobilized enzyme microreactor (IMER) was developed by using human-derived intestinal microsomes and characterized in the terms of enzyme immobilization yield and stability of enzyme activity. The microreactor was made from off-stoichiometric thiol-enes and microsomes were immobilized by fusion with previously immobilized biotinylated fusogenic liposomes being held in place via biotin-streptavidin interaction. A full potential of this platform was shown by enzyme inhibition mechanism determination, with performing only one experiment where feed solution containing different inhibitor concentrations in different time points was passing through the microreactor In addition, it was shown that CYP1B1 could be more expressed in HIM than it was previously reported.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Interdisciplinarne prirodne znanosti, Farmacija

POVEZANOST RADA