About the Project
The aim of this PhD project is to improve the treatment outcomes of HIV/AIDS by targeting the antiretroviral drugs specifically to the GALT. This will be achieved by design and synthesis of prodrugs of protease inhibitors and other antiretroviral agents with high potential for intestinal lymphatic transport. Intestinal lymphatic transport is governed by association of the molecules with chylomicrons in the enterocytes. An in silico model for association of drugs with chylomicrons will be used to evaluate the intestinal lymphatic transport potential of candidate molecules. Modifications of structures of protease inhibitors will be designed to yield prodrugs that possess the appropriate physicochemical properties required for efficient intestinal lymphatic transport following oral administration. The purified prodrugs will be assessed for the intestinal lymphatic potential by their degree of association with artificial chylomicrons-like emulsion (Intralipid®), and with natural chylomicrons separated from blood of human volunteers.
The pharmacokinetics and GALT biodistribution of the synthesised prodrugs and the corresponding active drugs will be assessed in vivo in a rat model. The antiviral activity of the drugs and prodrugs in the form that they appear in the GALT (associated with lipoproteins) will be assessed in vitro.
Finally, the in vivo efficacy of the proposed targeting approach will be assessed in a humanized mouse model of HIV infection.
The project will be supervised by Dr Pavel Gershkovich in the University of Nottingham, UK.
For informal inquiries please contact Dr Pavel Gershkovich ([Email Address Removed]).
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