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

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.

The key focus of the proposal is the introduction of a new material class and the demonstration of its utility in nanomedicine approaches - initially in improving HIV therapies. Additionally the programme will establish the British Society for Nanomedicine at a highly timely stage in the global investigation of nanotechnology in future therapy development.

The beneficiaries of the research therefore fall into a number of groups including scientists, clinicians, general public, patients and industry.

The introduction of a new class of materials has been shown many times to ignite new research concepts in fields that often span disciplines that are far removed from the original published concepts. The materials within this proposal are derived from branched polymers and this particular class of materials has shown many times that breakthroughs and new ideas may lead to new companies, commercial impact in existing industries (medicine/engineering/ nanotechnology/data storage/coatings to name a few) and enhance ongoing research programmes.

Within the field of nanomaterials and nanomedicine, a series of ongoing societal and governmental debates are discussing the safety and application of nanoscale technologies. Uniquely, this programme aims to introduce new nanomaterials, simultaneously evaluate the pharmacology and toxicology of the materials and establish the British Society for Nanomedicine to facilitate contact between researchers, academics/industry and regulators and engagement with the public. Collectively, this will have impact across pharmacology research, drug delivery, polymer materials and nanomaterials researchers. Importantly this proposal seeks to engage with regulatory authorities and generate real data that may impact future policy. We also aim to interact internationally to coordinate nanomedicine activities focussed on drug delivery.

The programme aims to generate therapy options that will be commercially protected and attractive for industrial exploitation. With the correct conversion of therapy options into medicines, the potential impact will spread to clinicians and HIV patients (in the first instance) to improve the care and outcomes within a disease that currently has killed over 25 million people and has 33 million living with HIV. The scale of the potential high impact on HIV patients arises from the need for high levels of patient compliance with therapies that require multiple pills to be taken several times each day over a lifetime. A positive impact on either the required dose of existing drugs, the number of tablets or the number of different drugs used would improve the quality of life for a large number of patients.

The materials proposed are covered by a patent filing that is owned by the University of Liverpool. It is expected that many more patents will flow that potentially will generate a significant commercial opportunity for the UK, initially through a spin-out company and later through production of medicine for international health benefits.

The project seeks to generate convincing chemical and pharmacological data over a 4.5 year period to allow commercial uptake towards the end of the programme. It is important to note that NO NEW DRUGS are being developed and therefore the new delivery vehicles may be seen as excipients for future drugs in mutliple disease areas. It is hoped that within 10 years of the start date, and supported by the critical early data and follow on research, Polydendrons may see themselves in early clinical trials.

Overall, the research proposed has the potential for multiple areas of impact. The researchers employed for the project will be highly trained during the research through exposure to multiple disciplines and therefore be extremely employable on conclusion of this initial research.