PhD Proposal Defense - Marilyn Allen

Location

Information Technology/Engineering : 456

Date & Time

May 31, 2019, 2:00 pm4:30 pm

Description

Nanostructures Encapsulating Antimalarial Drugs for Improved Systemic Lupus Erythematosus Treatment

Friday, May 31st at 2:00 p.m.
Information Technology/Engineering (ITE) Building, Room 456
Light refreshments will be provided.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease that attacks the body’s healthy tissues and organs, leading to organ damage such as lupus nephritis found in >50% of SLE patients. Circulating autoantibody and self-antigen (i.e. DNA) containing immune complexes activate plasmacytoid dendritic cells (pDCs) via toll-like receptors (TLR) -7 and -9 resulting in inflammatory type I interferon responses and increased disease activity.

Antimalarials, such as chloroquine, are TLR antagonists and the most commonly prescribed steroid-free disease-modifying anti-rheumatic drugs for SLE patients. However, antimalarials demonstrate delayed therapeutic activity and increasing toxicity with chronic treatment. We hypothesize that loading antimalarials in filamentous PEG-b-PPS nanostructures can halt inflammatory responses by delivering drugs directly to pDCs through passive shape-based targeting, resulting in limited toxicity, decreased disease progression, and increased drug activity per dose when compared to orally administered free drug. The specific aims of this project are (1) synthesize nanostructures with immunosuppressive activity against SLE-relevant pathways, (2) define nanostructure shapes that selectively accumulate in lupus-driving cells and organs in vitro and in vivo, respectively, and (3) test nanostructure efficacy in vivo using an environmental and a genetic mouse model of SLE. Results from this project will advance the field by defining nanostructure shapes that can target different cells and organs, and providing improved therapeutic options for SLE.