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

淋巴丝虫病是由寄生线虫感染引起的一种被忽视的热带疾病。成虫渗透淋巴系统，引起肿胀，而虫的后代在血液中循环。虽然一些治疗方法可以有效地杀死蠕虫后代，但由于成虫位于淋巴系统内，因此很难杀死成虫并彻底治疗该病。该项目将通过使用称为脂质体的微小脂基囊，在口服给药后更有效地将淋巴丝虫病药物输送到淋巴系统，从而帮助解决这一空白。这项工作将研究脂质体特性的变化如何影响药物进入淋巴和杀死成虫，从而使现有淋巴丝虫病药物更有效地应用。本科生将大量参与执行该项目，提供宝贵的研究经验。这项研究还将与实验室活动的发展相结合，如细胞培养方法、纳米材料和分析工具，以便在本科工程课程中实施。本项目的目的是开发淋巴丝虫病治疗的药物输送平台，优化从肠腔的淋巴药物摄取，增加成年丝虫病的杀灭，以提高淋巴丝虫病治疗的疗效。合成一组具有大小和电荷可控性质的脂质体，并对其对阿苯达唑、柠檬酸二乙基卡马嗪、多西环素等淋巴丝虫病药物的包封和释放进行表征。脂质体性质对其在肠上皮细胞中的转运以及随后药物有效载荷的淋巴通路的影响将通过肠上皮和乳管的体外模型进行研究。本研究还将探讨改变脂质体载体性质对体外治疗马来布鲁氏丝虫病成虫药物毒性的影响，为提高淋巴丝虫病治疗效果迈出重要一步。这些研究将阐明脂质体对口服给药后淋巴中药物浓度的影响，以及对寄生虫直接毒性的影响，从而有可能减少引起蠕虫死亡所需的药物剂量。这项研究还将与实验室活动的发展相结合，如细胞培养方法、纳米材料和分析工具，以便在本科工程课程中实施。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.