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

淋巴丝虫病是一种被忽视的热带疾病，由寄生线虫感染引起。成虫侵入淋巴系统，引起肿胀，而蠕虫后代则在血液中循环。虽然一些治疗方法可以有效杀死蠕虫后代，但由于其位于淋巴系统内，因此杀死成虫并彻底治疗该疾病更加困难。该项目将通过采用称为脂质体的微小脂质囊，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，从而帮助解决这一差距。这项工作将研究改变脂质体特性如何影响药物进入淋巴和杀死丝虫成虫，从而更有效地应用现有的淋巴丝虫病药物。本科生将积极参与该项目的执行，提供宝贵的研究经验。这项研究还将与细胞培养方法、纳米材料和分析工具等主题的实验室活动的发展相结合，以在本科工程课程中实施。该项目的目标是开发一种用于治疗淋巴丝虫病的药物递送平台，优化淋巴管从肠腔的药物摄取，增加对成丝丝虫的杀灭，从而提高淋巴丝虫病的治疗效果。将合成一组具有可控特性（包括尺寸和电荷）的脂质体，并将表征它们对淋巴丝虫病药物（如阿苯达唑、柠檬酸二乙基卡马嗪和多西环素）的封装和释放。将通过采用肠上皮和乳汁的体外模型来研究脂质体特性对其通过肠肠上皮细胞的运输以及随后的药物有效负载的淋巴通路的影响。这项工作还将研究改变脂质体载体特性对体外马来丝虫成虫药物毒性的影响，这是提高淋巴丝虫病治疗功效的重要一步。这些研究将阐明脂质体对口服给药后淋巴中药物浓度和直接寄生虫毒性的影响，从而有可能减少杀死蠕虫所需的药物剂量。这项研究还将与细胞培养方法、纳米材料和用于本科工程课程实施的分析工具等主题的实验室活动的发展相结合。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力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.