Site-Specific delivery of anti-infective therapies in neglected tropical diseases using nano-sized formulations

Student: Jennifer Woodring
Department: Chemistry
Advisor: Michael Pollastri

Abstract

Neglected tropical diseases are comprised of 13 parasitic and bacterial diseases. They put 2.7 billion of the world’s population at risk and their disability adjusted life years outnumber well known diseases like malaria and tuberculosis. There is a small financial incentive for pharmaceutical companies to pursue these diseases and this leads to very few drug candidates in the pipeline.

Human African trypanosomiasis, or African sleeping sickness, is a NTD disease that affects 36 countries in sub-Saharan Africa. It has a 100% fatality rate if not treated. There are only 4 drugs available for HAT: pentamidine, suramin, melarsoprol, and eflornithine. All 4 are expensive, not orally bioavailable, have severe adverse effects, require patient hospitalization, and are starting to show signs of resistance. Furthermore, melarsoprol has a 5% mortality rate due to its extreme toxicity. There is a dire need for new therapeutics, as well as better delivery systems for widespread distribution and patient compliance of these chemotherapeutics.

A recent study showed that when melarsoprol is complexed with cyclodextrin, not only was it orally bioavailable, but it was just as potent and less toxic to the animal models compared to regular melarsoprol dosing.

By encapsulating drugs into oil-in-water nanoemulsions or liposomes, we hope to increase the bioavailability of these current commercial drugs as well as our own NEU synthesized compounds. These nanoformulations could also have the potential to show less toxicity and better blood brain barrier penetration.