Preparació d'un connector sensible a dos valors de pH pel disseny de sistemes d'alliberament de fàrmacs

Author

Milà Bau, Clàudia

Abstract

Currently, one of the uses of the nanoparticles is as a possible drug transport vehicle, in this work a system that is sensitive to two determined pH values has been designed with the aim of transporting a drug and releasing it in a controlled and selective way in a given place.
To design this system tert-butyl 22-(9H-fluoren-9-il)-4,20-dioxo-7,10,13,16,21-pentaoxa-2,3,19-triazadocosan-1-oat has been synthesized which is the PEG linker attached to the mesoporous silica nanoparticle and which shows sensitivity at pH= 4,5 and 6,8. That means that at these two values of pH’s the system can be fractured.
In addition, an ester maleimide has also been synthesized which will serve to bind the BSA protein to the linker. This protein with the ester maleimide and the nanoparticle form together a protein corona, which is a kind of cover that changes the biological identity of the system. Less than 5% of the nanoparticles are not phagocytosed by the immune system of the human body and that is why the BSA protein is attached to the system, thanks to the behavior of this protein as a dysopsonine, the system is not detected and eliminated as a body foreign of the immune system.
When the system reaches areas close to the cells, is sensitive to different pH’s (4,5 and 6,8). Around the cells the pH is between 6 and 7 and the bond between the linker and the maleimide is broken at pH=6.8 therefore the system cand enter in the interior of the cell. Once inside the cell, in the endosome due to the pH=4.5 the bond between the linker and the nanoparticle is broken and the drug is released.

 

Director

Sánchez García, David

Degree

IQS SE - Undergraduate Program in Chemistry

Date

2021-09-07