PMBRC Technology Gateway Manager, Niall O’Reilly has contributed to the Technology Gateways blog with an article titled, “Efficient Drug Delivery”
For many of us, taking medicine is part of our daily routine. But have you asked yourself about the effectiveness of your medicine? Or whether the active ingredients are reaching the parts of your body where they’re needed most? Is there another, more efficient way to deliver the drug to where it’s needed? These are the questions being asked by the Pharmaceutical and Molecular Biotechnology Research Centre (PMBRC).
What is drug delivery?
Many of us take medicines as part of our daily lives without considering the technology embedded within the medicine. At the heart of any dose is the active ingredient or drug, but these are always formulated with a range of inactive ingredients which can play a crucial role in the functioning of the drug. Increasingly, pharmaceutical companies are employing advanced technologies to improve the therapeutic benefit to the patient. These technologies may prolong the release of a drug, improve absorption within the body, target the site of release and improve patient compliance.
Such approaches and technologies are generally referred to as drug delivery, and researchers in the PMBRC are working on a number of drug delivery projects. The aim is to tackle conditions which are poorly served by existing medicines on the market.
Poorly soluble drugs
To work, (nearly all) drugs must make their way into the body’s cells, which are composed largely of water. Increasingly however, promising molecules coming out of drug discovery labs are not very soluble in water. The formulation of these drugs poses a major challenge for the pharmaceutical industry.
One solution is to embed the drug molecules into polymer carriers. These carriers prevent the drugs from grouping together in clumps, called crystals, that can be very slow to dissolve. Through work funded by Science Foundation Ireland, PMBRC researchers are studying ways of dispersing poorly soluble drugs in such carriers. The researchers are also trying to understand why some polymers work better than others in improving drug solubility. Ultimately, these drug-polymers can be mixed into patient medicine.
Transdermal drug delivery
The skin is the largest organ in the body and as a result it should provide an excellent route for drug delivery. The skin, however, has evolved to keep things out, not let things in. Only a handful of drugs — nicotine, for example — have the precise chemical properties required to make their way through the skin’s various layers.
Since the first transdermal patch was approved in the late 1970s, fewer than 30 drugs have made it to market in this format. The PMBRC’s HIPODERM project is trying to address some of the problems associated with getting drugs across the skin. Funded by the EU’s Marie Curie Programme, HIPODERM is a consortium that includes Waterford-based EirGen Pharma Ltd, Cardiff University and An-eX Analytical Services Ltd (also based in Cardiff).
The drugs being evaluated in the project are highly potent. High potency drugs require only a tiny amount, often less than the weight of a grain of sugar, to have a therapeutic effect. However, exposure to large quantities of these drugs can be highly toxic or even fatal and specialist facilities, such as those at EirGen Pharma, are required to handle them.
As part of the project, PMBRC researchers have been working on delivering drugs for the treatment of non-melanoma skin cancers, one of the most common forms of cancer in Ireland. The goal here is to target the drug to the affected skin layer and avoid leakage into the bloodstream where they can cause unpleasant side effects.
Delivering biologic drugs
A spin-off from HIPODERM is a project looking at the delivery of biopharmaceutical drugs through the skin.
Biopharmaceuticals are drugs which are grown in living organisms (often bacterial or mammalian cells) before being harvested and purified. Biopharmaceuticals or biologics are big business: 5 of the top 10-selling drugs worldwide are classified as biologics. However, biologic drugs cannot be delivered orally (i.e. swallowed) as they are destroyed by the digestive system. Instead, most biopharmaceutical drugs are injected or delivered by intravenous infusion, which is inconvenient for the patient.
An alternative being explored by the PMBRC is to deliver these molecules transdermally using microneedle technology. Microneedles are arrays of miniature needles, less than a millimetre in length, which can penetrate the skin layers but are too short to hit pain receptors.
Funded by the Waterford Institute of Technology Postgraduate Scholarship scheme, PMBRC researchers are incorporating biopharmaceutical drugs into patches containing rapidly dissolving microneedle arrays. The microneedles dissolve deep within the skin, releasing the drug that can then make its way into the bloodstream.
Drug delivery to the eyes
There are a wide range of ocular (eye) conditions such as infections, glaucoma, dry-eye syndrome and age-related macular degeneration which require specialised drug delivery technologies. Currently, many of these conditions are treated with eye drops, but the eye has evolved a very effective tear and blinking system to remove foreign material (including drugs) from the surface of the eye. Consequently, eye drops must be administered frequently to be effective and often suffer from poor patient compliance, especially amongst the elderly.
Funded by Interreg IVA (Ireland-Wales Programme) and Science Foundation Ireland, researchers in the PMBRC are working on a number of drug delivery technologies to prolong the contact time between the drug and the surface of the eye. One of these approaches involves entrapping the drug in a contact lens which will slowly release the drug over a day or even weeks.
As well as improving the therapeutic effect of the drug, these formulations are expected to enjoy better patient compliance. Initial results have suggested that these technologies may even enable drug passage to the back of the eye. Currently, back of the eye conditions such as age-related macular degeneration must be treated by regular injections into the eye itself, an unpleasant experience with potential side effects.
Treatment of respiratory conditions
The lungs are a complex organ containing kilometres of airways and millions of air sacs. Delivering drugs deep into the lungs for the treatment of conditions such as asthma and chronic obstructive pulmonary disease (COPD) requires a complex marriage of chemistry, physics and engineering.
One approach is to use dry powder inhalers (DPIs). DPIs contain fine drug particles blended with a carrier material (usually lactose, the sugar present in milk). When the patient takes a breath, the powder is drawn through the mouthpiece of the inhaler. The turbulent flow of the powder causes the fine drug particles to detach from the lactose and they are carried into the lungs.
In order to work properly, the drug must stick to the lactose particles, but not adhere too strongly such that they do not detach on actuation. The physico-chemical properties of the drug and lactose are critical to getting this balance right.
Funded by Teva Pharmaceuticals in Waterford, PMBRC researchers are using a variety of techniques to probe the interactions between the drug and carrier. In particular, the researchers have been able to understand the effect of certain formulation and processing factors which affect the performance of the DPI device.
Depot injections for the treatment of chronic illness
There are many chronic medical conditions where patients are on medication over prolonged periods of time. The effective treatment of these conditions is dependent on the patient consistently taking their medication as directed by their doctor – something which many fail to do for a variety of reasons. If a GP could administer a dose to the patient which would slowly release the drug over a period of weeks, or even months, it would greatly aid in the treatment of their illness.
In collaboration with the SEAM research centre and two Waterford-based GPs, researchers in the PMBRC have identified one specific condition which is not adequately controlled with existing therapies and are working on a depot formulation which will release the drug over a period of at least two months. The work was initially funded by Science Foundation Ireland, but is now funded by the Enterprise Ireland Commercialisation Fund due to the commercial potential of the technology.