Eradicating HIV/AIDS by 2030 is one of the main goals of the World Health Organisation (WHO), which states that 40 million people are still affected worldwide. The first drugs to treat HIV were introduced in 1987, dramatically decreasing deaths and enabling patients to live a better quality of life. However, thirty years later, there is no vaccine and patient adherence to lengthy and complicated dosage regimens remains a key barrier to successful treatment. Patients are required to take multiple tablets over an extremely specific timeline. Most HIV drugs are eliminated from the body within hours, meaning daily dosing is essential to minimize the virus’ ability to mutate, whilst simultaneously developing a resistance to the medication. Missing even a single dose can seriously set back treatment.
Researchers from Queen’s University Belfast visited the ISIS Neutron and Muon Source to perform small angle neutron scattering on new hydrogel drugs to combat medical treatments. Dr Sreekanth Pentlavalli, together with PhD student Yuming An, from
Dr Garry Laverty’s group used SANS2D to study a new method of HIV treatment.
“Prior to visiting ISIS and ILL, we did not fully appreciate the potential to conduct pharmaceutical and health sciences research at these facilities. Upon seeing the cutting-edge instrumentation at ISIS and ILL, we realised their scientific support and unique capabilities could significantly advance our research” enthuses Dr Pentlavalli.
Dr Pentlavalli and his collaborators worked on the established HIV drug, zidovudine, linking it to a short peptide that they developed. They doctored the peptide so that, upon injection into the body, it is soluble, but once it meets certain enzymes in the body, they remove its watery properties, and enables systematic delivery throughout the body to prevent replication of the HIV virus.
Zidovudine would be transported as a freeze-dried powder that is readily formulated as a solution prior to injecting, allowing it to slowly dissolve and release within the body. Animal studies using rats revealed that the drug lasted in the blood for 35 days in comparison with another group given the standard zidovudine where it only lasted for six hours.
Also, one major advantage of the powder formulation is that it's easier to transport compared to current HIV drugs which can encounter difficulties in developing areas such as the African continent. Due to the hot climate, limited transport capabilities and inadequate storage conditions, the quality of the drug deteriorates, or it can even evaporate altogether.
With this recent visit to ISIS, Dr Laverty’s Group are simultaneously working on multi-drug delivery for both HIV and contraception. This technology may prevent sexual transmission of HIV from mother to child and unwanted pregnancy by inclusion of contraceptive drugs. They wish to understand the molecular structure of the treatment gels using SANS2D at ISIS as well as instruments at ILL before the gels can be tested in human clinical trials. Neutron scattering could reveal data behind the physical chemical properties of the gels and the Laverty Group hope to learn about any imperfections or potential improvements, to make them last even longer than 35 days.
This research initially began six years ago with sponsorship from the Wellcome Trust. There were many hiccups in the initial stages with sequences not being right for the gels and many modifications needed. Now with funding from EPSRC, the researchers are hopeful for the future where they see this method of treatment as a possibility for many other diseases such as cancer, tuberculosis and malaria.
“We believe this to be a platform technology, a basis for other medicines to last longer," Dr Pentlavalli enthused. “We also plan to explore the dimensions of our research for anti-psychotic drugs, which is particularly important as people, who need these drugs, forget to take their medications. Our next key area of focus will be tuberculosis and malaria and we will be returning to ISIS and ILL to test our platform.”
