Delivery Route Considerations for Designing Antigen‐Specific Biomaterial Strategies to Combat Autoimmunity

Abstract

Motivating the Development of Antigen-Specific ImmunotherapiesAutoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CD), and many others develop when the immune system mistakenly recognizes self-antigens as foreign, resulting in an orchestrated attack of host tissues. MS is a demyelinating disease that affects the central nervous system (CNS), RA is a chronic inflammatory joint disorder that can affect other tissues and organs, and T1D is a chronic condition whereby the pancreas produces little or no insulin. Complications from T1D can impact other tissues and organs. CD is a chronic digestive autoimmune disease that is triggered by gluten consumption, resulting in damage to the small intestine. The exact causes of autoimmune diseases are only partially understood. However, biological sex, [1,2] genetics, [3,4] existing autoimmune disease, [5] lifestyle (i.e., smoking, obesity, and exposure), [6][7][8][9][10][11] certain medications, [12] and certain infections [13][14][15][16][17] have been linked with the development of autoimmune diseases. For example, most autoimmune diseases affect more female than male patients, but the reason for this bias is unclear. [1] In MS, risk gene variant, HLA-DRB1*15:01, increases risk for patients, [18] and infection by Epstein-Barr virus (EBV) is associated with increased risks of MS, RA, and other autoimmune diseases. [13][14][15] These are currently no cures for these diseases, creating chronic battles that affect patient quality of life and require life-long compliance. Owing to the complex immunopathology of autoimmune disease, current treatments, even monoclonal antibodies, are not able to distinguish between normal and self-reactive cells. These therapies exploit distinct parenteral (e.g., intravenous [IV], subcutaneous [S.C.], intramuscular (IM), intradermal (ID), transdermal, intranodal) or mucosal (e.g., oral, intranasal (IN), pulmonary, sublingual, ocular) delivery routes to reduce disease severity. [19][20][21][22][23] For example, Ocrelizumab (Ocrevus, Genentech), a recombinant antibody that binds to CD20 on B lymphocytes to treat MS, is administered via IV injection and associated with risk of infections and allergic responses in certain patients. [19] Methotrexate, a first-line disease-modifying antirheumatic drug, is provided orally or S.C. but can lead to liver and lung damage and

Advances in dendritic cell targeting nano-delivery systems for induction of immune tolerance

“…The distribution and immunological effects of nanoparticles in vivo are influenced by different drug delivery routes ( Casey et al, 2018 ; Ackun-Farmmer and Jewell, 2023 ). Therefore, when delivering nanoparticles for disease treatment, it is equally important to select the appropriate therapeutic cargo as well as the suitable drug delivery route.…”

“…Nanoparticles loaded with immunomodulation drugs can be administered intravenously (IV), subcutaneously (SC), and intraperitoneally ( Dangkoub et al, 2021 ). IV administration is the most commonly chosen routes of nanoparticles administration, nanoparticles enter the circulation directly after administration, where they are almost entirely bioavailable in the bloodstream ( Ackun-Farmmer and Jewell, 2023 ). After IV administration, the nanoparticles can distribute and internalized by the APCs in the liver and spleens.…”