Studium interakcí antiretrovirálních léčiv s transportéry zajišťujícími příjem látek přes placentární mikrovilózní membránu
Latest statistical data (from 2015) show that nowadays approximately 77% of pregnant women infected with the human immunodeficiency virus (HIV) have access to antiretroviral therapy, enabling dramatic reduction in the number of children born with HIV. Exposure of fetus to antiretroviral drugs is considered advantageous, however, the mechanisms of transplacental transfer are still poorly understood. In spite of the protective efflux activity of ATP-dependent transporters, most antiretrovirals are able to cross placenta to a great extent and reach considerable drug concentrations in fetal circulation. The aim of our study is to assess whether materno-fetal transport of these drugs can be promoted by the solute carrier transporters SLCO4A1, SLC22A4/5, SLC38 and SLC7, expressed in the microvillous plasma membrane (MVM). Moreover, a spectrum of antiretrovirals will be evaluated for their ability to inhibit these transporters and thereby affect the materno-fetal transfer of essential molecules/nutrients. A combination of experimental models will be employed, including in vitro accumulation assays in human choriocarcinoma cell line BeWo and ex vivo uptake studies in MVM vesicles, fresh villous fragments and primary trophoblast cells isolated from human term placenta. The outcomes of this project could help optimize pharmacotherapy in pregnancy in terms of drug choice and dosage scheme.
Číslo:
GAUK1574217
Období:
01.01.2017 - 31.12.2019
Poskytovatel:
Univerzita Karlova - Grantová agentura UK
Hlavní řešitel:
Karahoda Rona PharmDr., Ph.D. - Farmaceutická fakulta v Hradci Králové
Celkový objem financí:
827 000,00 Kč
Interní řešitelé
Hlavní řešitel: PharmDr. Rona Karahoda, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Sára Karbanová, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: Mgr. Hana Horáčková, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: PharmDr. Lenka Ťupová, Ph.D.
- Farmaceutická fakulta v Hradci Králové, FaF HK
Spoluřešitel: doc. PharmDr. Martina Čečková, Ph.D.
- Univerzita Karlova,
Školitel: prof. PharmDr. František Štaud, Ph.D.
- Univerzita Karlova,