Towards NanoMedicine Interventions for HIV/AIDS

Nanomedicines have proven extremely valuable in recent years and many are used daily to treat patients with a range of conditions or needs - from the treatment of cancer and menopausal symptoms to the prevention of organ rejection or malnutrition/weight loss. A range of unmet clinical needs may benefit considerably from the research and application of new nanoparticle synthesis techniques and the development of appropriate nanomedicines and provision of scale-able, commercially viable technologies that can impact patient outcomes is a key goal of nanomedicine research.

Validation of new technologies through optimisation of product performance, demonstration of pharmaceutically relevant manufacturing and in-man pharmacokinetic studies is critical for progression as is the study of nanotoxicology to establish a safety assessment that supports future investment.

To date, a series of candidate nanomedicines for HIV/AIDS treatment have been generated at the University of Liverpool in collaboration with IOTA NanoSolutions Ltd, a specialist start-up company in the UK, and supported by RCUK funding. IOTA is commercialising a novel nanoparticle synthesis technology (initially developed at UoL with EPSRC funding support) that rivals the most successful commercial top-down nanomedicine technology - nanomilling. The HIV/AIDS nanomedicine candidates have been the subject of 3 patent filings and funds are sought to optimise their production and establish their behaviour using clinical research techniques. Additionally the project will seek to dramatically increase the understanding of nanomedicine through fundamental mechanistic studies, thereby producing new insight into the mode of action and the safety of future nanomedicines.

If successful, the programme will produce the first nanomedicine options for HIV/AIDS therapy with benefits for patient care potentially including lower dosing, reduced side effects, better patient-to-patient consistency and a reduction of tablet size. Significant interest has been generated within Medecins Sans Frontiere who are keen to utilise the outputs for charitable medicines in the developing world, treating children with HIV infection with better products and prevent HIV infection in newborns. Currently, to prevent transmission of HIV to children from infected mothers, the World Heath Organisation has recommended dosing from 3 weeks after birth with antiretrovirals. The only children's medicines available include high levels of alcohol to dissolve the poorly water-soluble drugs. The nanomedcines within this programme are dispersible in water and offer a step-forward in paediatric therapy.

The successful establishment of the fundamental research underpinning new nanomedicines will provide a clear advance in the UK's global standing in this emerging area, currently valued at >US$75bn and growing rapidly, with expectations to reach >US$100bn within 3 years.

The key focus of the proposal is the collaborative progression of research outputs from RCUK Grand Challenge funding to demonstrated nanomedicines with the potential for further development into products and the delivery of improved patient outcomes. Critical to this is the generation of in man PK data as this validates the research by generating relevant evidence of behaviour in man rather than questionable links from animal models to human performance.

The beneficiaries of the research therefore fall into a number of groups including scientists, clinicians, patients and industry. Within the field of nanomaterials and nanomedicine, a series of ongoing societal and governmental debates are discussing the safety and application of nanoscale technologies. The programme will engage fully with this debate and provide insight and new opinion from the direct outputs of the materials, pharmacology and clinical research proposed, with the potential to impact policy decisions.
The charity Médecins Sans Frontière and the Drugs for Neglected Diseases Initiative are highly committed to evaluating the nanomedicine options for the paediatric dosing in the developing world. This holds the possibility of prevention of mother-to-child transmission as the WHO guidelines recommend a prophylactic dosing of antiretrovirals to new-borns as early as 3 weeks old and for up to 8 years. Provision of relevant formulations has been poor and new options are urgently required to prevent transmission during breastfeeding and into the later years. Adoption of the proposed research outputs in sub-Saharan Africa would impact a growing population of HIV patients and help to slow the increasing numbers of infant infections. Within developed countries, HIV nanomedicines may act to increase patient
compliance and reduce patient variability, thereby providing clinicians with therapies with more predictable clinical outcomes and consistency across varying patient populations. Also, it is a fallacy to believe that HIV is not a concern within the developed world and can be managed as a chronic disease. Infections in teh UK continue to rise alarmingly and maintenance of patient quality of life requires a life-long commitment to a cocktail of drugs with considerable inter-patient variability and side-effects. Although the rate of infection has decreased, the numbers of new infections per year in the UK-alone are still in the thousands and multi-drug resistance (often derived from poor patient compliance) is leaving many patients with fewer therapy options.

If successful, the project will generate therapy options that will be commercially protected and have considerably demonstrated progress towards product manufacture, thereby able to generate future investment. The provision of new data and successful results in this area will show the wide applicability of the nanoparticle synthesis and resulting nanomedicine generation. The project also has the capability to secure the future of a small, high technology company in the North West, building a foundation for considerable investment and commercial revenues. It is also worth noting that outputs from the programme will potentially represent the first nano-antiretroviral commercial therapies after progression to the clinic.
As a platform for future products with a developed supply chain and demonstration of in-man pharmacokinetics, this will generate a significant commercial opportunity for the UK with multiple areas of impact.