Engineered biomaterials for drug delivery and therapeutic modulation in lymphatic tissues
Loading...
Author(s)
Sestito, Lauren Faith
Advisor(s)
Editor(s)
Collections
Supplementary to:
Permanent Link
Abstract
The lymphatic system plays a critical role in both fluid balance and the immune response, and its dysfunction is implicated in a wide variety of pathologies including cardiac disease, cancer, and lymphedema. While this makes lymphatic tissues promising therapeutic targets, lymphatic drug delivery is challenging as small molecule drugs show poor lymphatic vessel uptake by any delivery route. Once drugs have entered lymphatic vessels, access to therapeutically relevant cells within the lymph node is further restricted by cellular and physical barriers. There is a clear need for delivery methods to enhance drug access to therapeutic targets in lymphatic tissues, including both lymphatic vessels and lymph nodes. As such, the overall objective of this work was to employ engineered nanoparticle systems to enhance and control drug delivery to the lymphatics to enable the study and therapeutic modulation of 1) the lymph node and lymph node-resident cells and 2) intrinsic pumping in collecting lymphatic vessels. To this end, two nanoparticle platforms were advanced: one in which the highly reactive small molecule nitric oxide was chemically conjugated to nanoparticles and applied to modulate macromolecule penetration into lymph nodes, and one in which a calcium channel modulator was encapsulated and applied to improve lymphatic vessel pumping function for the treatment of lymphedema. This work revealed the benefit that biomaterial platforms provide to enable small molecule delivery to lymphatic tissues and the versatility of the employed nanoparticle platform, developing both a mechanism for enhancing drug access to typically restricted cells in the lymph node and a novel treatment for lymphedema and other diseases characterized by lymphatic dysfunction.
Sponsor
Date
2021-04-27
Extent
Resource Type
Text
Resource Subtype
Dissertation