By Andrew Owen, University of Liverpool
While scientists develop new drugs to treat a multitude of conditions, nanotechnology is pushing the boundaries of how we deliver them to patients – targeting delivery to cancer cells and giving a drug dose once a month rather than every day.
Using nano-sized carriers to deliver medicine has been around for some time. Nearly 20 years ago chemotherapy drug liposomal doxorubicin (brand name Doxil in the US) was approved for treating Kaposi’s sarcoma, a rare cancer often found in patients with AIDS. The molecules of the anti-cancer drug doxorubicin are held in a liposome, a fatty particle, that allows the nanomedicine to last longer in the body. And liposome technology has been available since the 1960s.
But nanotechnologies are continually evolving, as are their applications and the sophistication of treating and diagnosing disease.
Solid or carrier
In broad terms, nanotechnology in drug delivery involves either forming solid drug nanoparticles or loading the drug into nanocarriers that improve how a medicine is distributed in the body. One of the latest offerings is an experimental injectable “smart sponge” that expands and contracts in response to blood sugar levels to release insulin within diabetic patients as needed.
Solid drug nanoparticles are typically made by taking large chunks of water-insoluble drugs and grinding them into particles with diameters measurable in 100s of nanometers, with each particle about one millionth the size of a tennis ball. There are now numerous examples of these formulations that have been licensed as safe and effective for treating diseases ranging from organ rejection, cholesterol reduction, schizophrenia, chronic pain and inflammation.
Until recently, the primary aim of solid drug nanoparticles was to improve the delivery of drugs taken by mouth; by increasing the amount of drug that is able to cross the intestinal barrier and enter the bloodstream. But recent work, in the area of HIV, has been about developing ways to take medicines less frequently – for example as little as once a month or even longer using a solid drug nanoparticle depot that is injected into muscle. This kind of work may make it easier for people with HIV to manage their treatment.
Recent work at Liverpool University with solid drug nanoparticles could reduce the doses required for orally administered HIV drugs and Phase I clinical trials are now being planned.
A less toxic payload
Doxil is a nanocarrier-based medicine, where a particle of fat (a liposome) is the carrier. But there are a plethora of different nanocarriers at various stages of development. They range from various polymeric nanoparticles, nanoemulsions and inorganic materials such as gold or silver nanoparticles.
The majority of nanocarrier-based medicines are being developed to treat cancer and are generally injected directly into the blood. Their benefits stem from their ability to target certain areas of the body. By increasing the amount of drug at the target and reducing it in other tissues, these nanomedicines reduce the toxicity that occurs when the drug is more widely distributed in the body.
Almost all nanocarrier-based medicines in development involve either passive targeting or active targeting. In cancer, as solid tumours grow and expand they disrupt the tissue that surrounds them creating nano-sized pores that allow medicines like Doxil to leak through and penetrate the tumour. But in healthy tissue the barrier remains intact and prevents the accumulation of the nanocarrier. Imagine the tissue around the tumour is like a net while the tissue around healthy tissue is like a cloth. Both net and cloth will let water through (dissolved drug in a conventional form) but only the net (tumour) will let through sand (nanoparticles).
The ability to capitalise on an inherent process in this way is called passive targeting. And recent research into amplifying this passive targeting alongside active targeting has shown promising data. Usually, this involves modifying the nanoparticle surface to add a targeting ligand, a structure that can specifically recognise features of diseased cells. This specifically homes the medicine to the target cells. One of the first actively targeted nanomedicines, BIND-014, recently entered into Phase II clinical trials.
Although most of these nanomedicines are used in cancer, other examples are being used to treat conditions from multiple sclerosis to infectious diseases. For example, Ambisome, another liposome-based medicine that contains the drug amphotericin B, is effective at eliminating fungal infections but is less toxic, again because of its favourable distribution in the body.
Nanoparticles have long been known to have optical properties. Many of the colours within medieval stained-glass windows were produced using nanoparticles of inorganic materials such as silver and gold. These nanoparticles are so small that they are able to interfere with the wavelength of the light that hits them due to a process we now know of as surface plasmon resonance.
The potential application of these optical properties for the diagnosis and monitoring of diseases have recently been attracting interest. For example, certain nanoparticles are able to selectively accumulate within tumours and the optical properties allow them to be seen using external equipment.
More recently, nanotheranostics (a combination of nano, therapy and diagnostics) have attracted attention for their potential to not only enable us to see disease tissue but to simultaneously deliver a drug payload. In cancer treatment this would allow doctors to treat patients and study the cancer at the same time.
Andrew Owen is the co-inventor of patents related to HIV nanomedicines