Hydrogel Microparticle Networks for the Controlled Delivery of Nanomedicines

This proposal seeks to combine the advantages of nanomedicines with the proven benefits of sustained drug release, addressing a global unmet need. This will be achieved through the design and development of a new type of implantable drug delivery system which releases drug-containing nanoparticles into the circulation. Such a technology would offer vast benefits for those patients who require long-term treatment. By combining recent developments in materials science, materials chemistry and nanomedicine, options will be studied that may act as future platforms for implantable nanomedicine release systems.

Poor compliance, the improper following of a doctor's treatment recommendations is expected for 50% of patients suffering from chronic diseases. The resulting implications of poor compliance are increased ill-health, increased likelihood of negative consequences and the possibly of the disease developing a resistance to the treatment. Poor compliance is a very serious problem, it has been estimated that in the European Union 194,500 deaths a year can be attributed to poor compliance.

It is possible to entrap a drug within a material, which can then be implanted in the body to slowly release the drug. Such materials are known as implantable drug delivery systems and can be designed to give sustained drug release over extended periods of time, therefore removing the need for the patient to take repeated drug doses. Implantable drug delivery systems have been shown to be medically very successful in the delivery of contraceptives and for the treatment of a range of diseases including cancer. In addition to removing the problem of poor patient compliance, implantable drug delivery systems can be configured to release drug directly into the surrounding tissue avoiding one of the main issues with orally taken drugs that are prevented from reaching blood circulation (first pass metabolism). In general, patient groups that suffer from poor compliance welcome implantable devices that aid the attainment of positive outcomes from their therapies.

While implantable drug delivery systems have been demonstrated for the release of conventional drugs such as small molecules and biopharmaceuticals, release of drugs in the form of nanomaterials (materials with one dimension less than 1000 nm) from implantable drug delivery systems has never been demonstrated. The use of nanomaterials to deliver drugs is known as Nanomedicine, a field that has undergone rapid growth in the past decade. The vast majority of nanomedicines are administered to patients intravenously or orally and therefore currently need to be repeatedly re-administered to maintain the correct drug concentration in the body. Nanomedicine has been found to offer numerous advantages in therapeutic treatment, derived from the properties of the nanomaterials; including enhanced uptake of the drug into the blood stream, reduced side effects and improved delivery of the drug to where it is needed. Currently there are over 40 nanomedicines in clinical use, and over another 100 nanomedicines in medical trials. It is therefore likely that the use of nanomedicines will become more widespread in medicine in the future.

This proposal aims to provide a proof of concept system to address the serious issue of poor patient compliance, for the delivery of present and future nanomedicines, with the goal of attracting further developmental and research activities in order to progress towards actual patient benefits.

The key focus of this proposal is the design and synthesis of a proof of concept platform technology; a system based on hydrogel microparticle networks that allow the tuneable controlled release of nanomedicines. Once this hypothesis has been proven, further research can be undertaken to develop systems for applying controlled release of nanomedicines to specific diseases. The impact of this proposal covers a range of economic and societal beneficiaries.

Economic:
The results of this work will be commercially protected where appropriate and future proposals will build on this research with potential to generate a significant commercial opportunity for the UK. These opportunities will initially arise either through a spin-out company (UoL has a history of spin out activities) or through direct engagement with industry. Future value will be derived from the production of a series of medical devices, tailored to specific clinical needs within different diseases that may be sold internationally.

Societal:
The ability to produce long-term sustained release of nanomedicines impacts heavily on healthcare, the issue of poor patient compliance can be avoided with its associated increased morbidity and mortality rates (an estimated 194,500 deaths a year in the EU). Further societal impact may be realised by applying the controlled release system to a range of acute and chronic conditions including infectious disease and long term disorders. For example antipsychotic nanomedicines have a direct compliance issue and maximising treatment adherence in psychotic patients would help to avoid associated violent crime and suicide risks associated with schizophrenics.