New Branched Polymers Excipients and Emulsions for Enhanced Drug Delivery

The poor absorption of many orally-dosed medicines results in the use of higher doses per administration than would be ideally delivered to maintain lower production costs, storage issues, and manufacturing capacity. For HIV and other chronic diseases, patients require a life-long commitment to therapy meaning that costs accumulate over time. This has considerable impact in low- and middle-Income countries where many chronic infectious diseases require lifelong dosing to minimise further spread and maximise the quality and length of life for infected patients, which has a knock-on effect for productivity and wider economic considerations. HIV is a specific example where doses greater than 900mg per-patient-per-day are common, leading to a considerable cost burden for healthcare providers (often local governments as well as the international community) and the prevention of wide spread access to therapy due to cost constraints. In many cases, these high doses are only required because a limited amount of the drug that is swallowed actually enters the bloodstream to provide the explicit pharmacological benefits. In some cases, the drug that stays in and passes through the gut may cause the patient considerable side-effects such as gastrointestinal disturbances. Within this grant we aim to progress a new approach to therapy formulation through to demonstration of actual benefits in healthy volunteers and establish the potential to reduce administered doses whilst maintaining the amount of drug available within the bloodstream to exert its therapeutic effect after oral dosing.
This will require the full demonstration of the potential to take our new materials technology through to pharmaceutical and regulatory approved manufacturing processes and use the material to generate a new therapy candidate. After approval for human pharmacokinetic evaluation, a small study will establish the data required to de-risk pharmaceutical and material industry investment to develop new medicines. The proposed research, therefore, considerably accelerates the outcomes of previous research towards actual impact that could provide healthcare benefits around the world. While the programme is specifically targeted at a new HIV medicine, we expect the validated platform technology to be widely applicable across indications, saving costs of treatment, enabling delivery of drugs that could otherwise not be delivered orally, and generating wealth for the UK economy through commercialisation in high income contexts.

The introduction of new pharmaceutical excipients and the clear demonstration of their value and benefits may impact widely upon academia and industry, thereby having demonstrable scientific, economic and societal benefit. Academically, new approaches to drug delivery with clear evidence of benefits in human studies are well known to spur considerable new activity and investment. The combination of concepts used within the translational pathway outlined in this research is potentially highly synergistic, encouraging researchers to engage in translation and deliver new impact through material developments that may be progressed through relevant manufacturing processes. As such, the strategy for taking model systems with academic proof-of-concept through to actual healthy volunteer demonstration will inspire other researchers to progress their healthcare innovations and create evidence that will de-risk their engagement with pharmaceutical companies and development partners alike.
Achieving matching PK from reduced concentrations of drugs in orally administered therapies has the potential to revolutionise healthcare system costs for a range of diseases, but specifically the growing cost for treatment of chronic indications. The value for HIV alone is huge (see letters of support), but a validation of the core technology opens opportunities for much more widespread uptake, and will enable us to generate additional impact from engagement with our existing (and new) commercial partners. In addition, the dossier of information generated for the new copolymer excipient will make this material a viable and scale-able option for wider provision to the drug formulation community - pharmaceutical excipients are predicted to reach an estimated $8.1bn dollar global market in coming years, thereby providing an exciting opportunity for a material company to exploit. The interest in this market is clear from the engagement of Itaconix in this programme, and if successful this offers an opportunity for a UK company to learn more within this expanding market.
It is expected that the research presented here may impact on a wide range of communities and, eventually, offer financial, economic and societal benefits. Through careful selection of the candidate therapy, the pharmacological target and the oral administration route, the team have shortened the pathway to clinical impact to potentially as little as 2 years post completion of this research - a clear acceleration of healthcare impact from initial fundamental research, which is only possible because of the foundations set by our previously EPSRC-funded research.
The laboratory researchers involved in this study will witness the translation of novel concepts through to industrial evaluation and scale-up and evidence formation through healthy volunteer studies. It is our strong hope that the impact of experiencing translation of their research will help further cement the need for truly interdisciplinary and ambitious research in the next generation of UK scientists.