New Nanoscale Drug Delivery Systems and their Application to HIV/AIDS treatment

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HIV/AIDS is described by the World Health Organisation as a global pandemic. Estimates show that over 25 million people have died since 1981 and over 33 million people including adults and children are currently living with the disease. In 2005, AIDS claimed an estimated 3.3 million lives globally, including more than 570,000 children. The prevalence of HIV/AIDS continues to increase and it is expected that over 90 million will ultimately be infected in Africa alone. The UK had the highest growth in HIV/AIDS infection in western Europe in the period between 2001 - 2007 with a 64% increase. HIV treatment suffers from many issues including the need for patient compliance with a very strict regime of medication. HIV mutation leads to resistance to existing therapies but the ability of therapies to target HIV in the body is critical to the success of medication. HIV resides in various sites throughout the body but there are both cellular and tissue sites which are particularly difficult for drugs to reach. These so called 'sanctuary sites' have the potential to be targeted by particles of drug, rather than dissolved drug molecules. Cancer research has shown the benefits of particulate nanomedicine drug delivery approaches. The use of nanoscale polymer carriers which act as vehicles to transport and deliver poorly soluble drugs to the desired site of action, has been beneficial for tumour targeting as the particle nature of the nanomedicine drives the accumulation in tumour tissues. Cellular and tissue sanctuary sites in HIV infection have been widely speculated to also be ideal candidates for particle-based approaches but there has been limited work in this area.Branched polymers may operate as particle-like drug delivery vehicles and many have been shown to have therapeutic advantages. The best materials are however very expensive to synthesise and would not be viable for treatments in populations such as the sub-Saharan regions (over 20 milllion HIV infections) where cost is a critical component of treatment choice. The University of Liverpool has developed a new class of materials, Polydendrons, that offer many of the benefits of the most sophisticated branched polymers, but can be produced relatively cheaply. In early work, prototype materials have been produced with particle sizes of >40nm and encapsulation capabilities. These materials are unique and still at a very early stage of development. This proposal will simultaneously explore the synthesis of Polydendrons and their ability to intervene in HIV treatments. They will be studied as drug carriers of specific size, shape and surface functionality and their ability to target HIV in sanctuary sites will be established. A collaboration between the departments of Chemistry and Molecular and Clinical Pharmacology over 4.5 years is proposed with input from global pharmaceutical companies and HIV clinicians. This approach of material synthesis with integrated pharmacology will considerably accelerate the development of potential new therapies leading to a leading position for the UK that will be applicable to other health issues such as cancer, tuberculosis and hepatitis C.