Amoebic parasitic infections are widespread in the tropics. Amoebic dysentery can be fatal if the parasite progresses to the brain. Treatment normally involves antimicrobial drugs but some of these such as metronidazole are also effective against bacteria their use can add to antibiotic resistance. Usually the organism spends much of its life cycle in the gut and galactose receptors allow it to bind to the wall of the intestine. Major difficulties occur when the amoeba pass through the intestine. An alternative is to provide a nanoparticle or polymer functionalised with galactose that can compete with the galactose on the intestine wall. This would maintain the organisms in suspension and allow the body to excrete them, removing the parasite from the patient.
This project addresses this idea by providing polymer materials that bind selectively to the amoeba and then respond to their presence by changing conformation. We have applied a similar approach to remove bacteria from wounds.1-4 The change in conformation can then be assessed using dyes that are sensitive to their environment. We will work in collaboration with parasitologists at the Indian Institute of Technology (IIT), Kharagpur, who will test the polymers in established microbiological assays. The key polymers are highly branched poly(N-isopropyl acrylamide)s with binding ligands at the chain ends. The ligand in this case will be either galactose or mannose. Galactose if known to bind to the target amoebae, which also are functionalised with mannose receptors.
The project will mainly involve the synthesis of these polymers and their characterisation in terms of molecular structure and physical properties with their microbiological properties being assessed at IIT Karagpur. We will also examine the toxicity of the polymers in cell culture assays at Bradford.