Ultrasound and heat-sensitive capsules boost targeted drug delivery
The Phase I study saw 10 patients, with inoperable primary or secondary tumours in the liver who had previously received standard treatment, be given doxorubicin encapsulated in lipid drug carries (liposomes).
The capsules are heat-resistant at body temperature, but when ultrasound is used to target tumours – heating the area to over 39.5°C – the liposomes breakdown to deliver their payload.
We spoke to lead author of the study Paul Lyon, academic clinical fellow in radiology at The Institute of Biomedical Engineering, about why this form of drug delivery is a step forward: “Solid tumours…can be difficult to treat by systemic chemotherapy alone, not least due to high interstitial tumour pressures which make it difficult for the drug to enter the tumour at therapeutic levels. Combination chemotherapies over multiple cycles are typically used in an attempt to increase the levels of cytotoxic drugs delivered to the tumours whilst balancing unwanted side effects.”
He continued, “The combination of focused ultrasound and ultrasound-activated nanoparticles is an attractive solution to drug delivery, as enhanced intratumoural drug levels may be achieved in a highly targeted manner, both non-invasively and without the use of ionising radiation. Further, such targeting has the potential to lower the amount of dose reaching healthy tissues, which also reacts to chemotherapy and causes side effects, thus widening the therapeutic window.”
Beyond being more targeted and minimising the side-effects, the study noted that seven out of 10 patients displayed increased drug delivery into tumours by between two- and ten-fold.
The advantages of this were highlighted by Lyon, “Highly targeted chemo-ablation of liver tumours can be achieved after a single cycle of LTLD [Lyso-Thermosensitive Liposomal Doxorubicin] at standard doxorubicin dose, even in tumour subtypes such as colorectal tumours, which are classically thought of as being resistant to doxorubicin.”
The next step for research will be further clinical tests for this form of drug delivery before lining up the technique to be used in a head-to-head comparison with standard treatment. Lyon predicts that we could see focused ultrasound becoming routine treatment for targeted drug delivery across a number of different oncology indications in the years to come.
The research is one in a number of research projects being done to utilise nanotechnology to advance drug delivery, with nanoscale silica cages being developed to carry sensitive drugs to target areas and greater commercial interest in protecting such delivery methods.
