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Targetted and Sustained Drug Delivery to the Eye
Glaucoma and trachoma are leading causes of blindness worldwide, with a combined >200M people affected and close to 10M at immediate risk of permanent sight loss. For both diseases, surgical treatment success is directly dependent on the avoidance of postoperative scarring. However, there is no treatment to prevent scarring in trachoma and the current drugs used to prevent scarring following filtration surgery for glaucoma can have serious blinding side effects. We have designed an innovative product consisting of biodegradable microspheres loaded with doxycycline, a common drug, for local delivery at the time of surgery to achieve safe, targeted and sustained anti-scarring action. These have shown remarkable anti-scarring efficacy in laboratory tests. We now aim to develop this treatment towards clinical trials, with a potential benefit to millions worldwide.
People involved:
Professor Richard Day
Professor Maryse Bailly (UCL Institute of Opthalmology)
Professor Sir Peng Khaw (Moorfields Eye Hospital)
Professor Matthew Burton (London School of Hygiene & Tropical Medicine)
Elif Gokoglan (PhD student)
Cancer Therapy
Prostate cancer is a leading cause of mortality in men. About 9,000 men undergo radical prostatectomy every year in the UK with 10-20% requiring adjuvant or salvage (radiation) therapy or use of systemic chemotherapy drugs. Failure can occur because cancer cells are shed during surgery, incomplete excision or metastatic disease. Adjuvant or salvage therapy confers additional harm through collateral damage to the bladder, urethra and rectum, whilst administration systemic chemotherapy drugs often results in significant toxicity and harmful side effects.
We are developing a novel approach that combines surgery with precise delivery of anti-cancer cytotoxic therapy immediately after prostate removal. This will be achieved through a unique combination of degradable microspheres loaded with a chemotherapy drug (see publication). When implanted into the tissue cavity left following tumour removal, the microspheres elute drug in a controlled manner to target cancer cells, whilst avoiding collateral tissue damage and toxicity associated with systemic delivery of chemotherapy drugs (see publication).
This Cancer Research UK-funded project is investigating combining docetaxel, a clinically approved anti-neoplastic drug, with a new class III implantable scaffold consisting of TIPS microspheres that we have already validated for clinical testing. This approach is novel and potentially transformative.
People involved:
Professor Richard Day
Professor Hashim Ahmed, Imperial College London
Developing Nanogel Drug Delivery Systems
Intrapericardial drug delivery is an uncommon route where drugs are administered directly into the pericardium, a bilayered sac surrounding the heart that possess several physiological functions (see review article). The space enclosed by the pericardium (known as the intrapericardial space) contains about 20-40 mL of fluid. Owing to its proximity to the myocardium and slow clearance, this space could be employed for the delivery of cardioprotective agents to treat myocardial infarction. The project combines advances in polymer engineering and nanotechnology with an analytical Quality by Design (QbD) strategic approach (see publication) to engineer a formulation system that can deliver cardioprotective drugs to the infarcted myocardium via the intrapericardial space.
This EPSRC-funded project utilizes established processing technology to produce polymer based nanocarriers that contain cardioprotective agents for intrapericardial administration. Release of the cargo is dictated by degradation of the polymer and/or diffusion, which can be moderately refined depending on the molecular mass of the polymer, particle size, shape and porosity (see publication).
In addition of ischaemic heart disease, it is anticipated that the new technology will be applicable to other diseases where controlled release of drugs will be beneficial.
People involved:
Dr Kenneth Ho
Professor Richard Day
Professor Duncan Craig, UCL School of Pharmacy