ERI: Development of a Liposomal Platform for the Treatment of Lymphatic Filariasis

点击翻译按钮获取中文摘要

Lymphatic filariasis is a neglected tropical disease caused by infection with parasitic nematodes. Adult worms infiltrate the lymphatic system, causing swelling, while worm offspring circulate in the blood. While some treatments effectively kill worm offspring, it is more difficult to kill adult worms and thoroughly treat the disease because of their location within the lymphatic system. This project will help to address this gap by employing tiny, lipid-based sacs called liposomes to deliver lymphatic filariasis drugs to the lymphatic system more effectively after oral administration. This work will investigate how changing liposome characteristics affects both drug access to lymph and the killing of adult filarial worms, resulting in a more effective application of existing lymphatic filariasis drugs. Undergraduate students will be heavily involved in executing this project, providing valuable research experiences. This research will additionally be paired with the development of laboratory activities on topics like cell culture methods, nanomaterials, and analysis tools for implementation in undergraduate engineering courses. The objective of this project is to develop a drug delivery platform for the treatment of lymphatic filariasis that optimizes lymphatic drug uptake from the intestinal lumen and increases adult filarial worm killing to improve the efficacy of lymphatic filariasis therapy. A panel of liposomes with controllable properties including size and charge will be synthesized, and their encapsulation and release of lymphatic filariasis drugs like albendazole, diethylcarbamazine citrate, and doxycycline will be characterized. The impact of liposome properties on their transport by intestinal enterocytes and subsequent lymphatic access of drug payloads will be investigated by employing in vitro models of the intestinal epithelium and the lacteal. This work will also investigate the impact of changing liposomal vehicle properties on drug toxicity against adult Brugia malayi filarial worms in vitro, an important step to improving lymphatic filariasis treatment efficacy. These studies will elucidate liposomes’ impact on drug concentration in lymph after oral administration and on direct parasite toxicity, potentially enabling a reduction in drug dosing required to elicit worm killing. This research will additionally be paired with the development of laboratory activities on topics like cell culture methods, nanomaterials, and analysis tools for implementation in undergraduate engineering courses.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.