Skip to Main content Skip to Navigation
Theses

Vectorisation du ganciclovir par des cyclodextrines - Etudes des complexes supramoléculaires et de l'activité antivirale sur des modèles cellulaires et murin infectés par un cytomegalovirus

Abstract : The antiviral chemotherapy has strongly grown in the last decades and new drugs are currently available for the treatment of viral diseases. Nevertheless, problems such as toxicity of treatments and emergence of resistant viral strains still occur. In the case of Human Immunoodeficiency Virus and herpes virus, including human cytomegalovirus (HCMV), infections, problems such as chronic treatment add. In arder to limit these drawbacks, we studied vectors able to carry antiviral molecules and thus to improve their pharmacological properties. The vectors used were cyclodextrins (Cds) which are neutral saccharides forming a cage in which a wide range of drugs can be encapsulated and hence have their absorption and therapeutic efficiency improved. We studied through Nuclear Magnetic Resonance and spectrometry the ability of three native Cds, [alpha]-,[beta]- and [gamma]-. Cds, to form inclusion complexes with ganciclovir (GCV), an anti-HCMV agent. We tested the influence of these Cds on the in vitro antiviral activity of GCV against various HCMV strains. Only [beta]-Cd was able to form a complex with GCV and we demonstrated that it could improve the in vitro antiviral activity, of GCV. In order to test the influence of complexation of anti-HCMV molecules on their in vivo antiviral activity, we developed a murine model of cytomegalovirus infection. We then determined the experimental conditions of the infection and evaluatecl the infectiosity of the virus in mouse organs according ta time. In this in vivo model, we carried out preliminary studies on the antiviral activity of complexed GCV with [beta]-Cd, which revealed an improvement of its efficiency.
Document type :
Theses
File URL :
http://docnum.univ-lorraine.fr/prive/SCD_T_2000_0321_NICOLAZZI.pdf
Complete list of metadata

https://hal.univ-lorraine.fr/tel-01746922
Contributor : Thèses Ul Connect in order to contact the contributor
Submitted on : Thursday, March 29, 2018 - 10:47:50 AM
Last modification on : Friday, February 26, 2021 - 3:24:03 PM

Identifiers

  • HAL Id : tel-01746922, version 1

Collections

Citation

Céline Nicolazzi. Vectorisation du ganciclovir par des cyclodextrines - Etudes des complexes supramoléculaires et de l'activité antivirale sur des modèles cellulaires et murin infectés par un cytomegalovirus. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2000. Français. ⟨NNT : 2000NAN10321⟩. ⟨tel-01746922⟩

Share

Metrics

Record views

33