Combinatorial drug delivery approaches for immunomodulation

Abstract

Immunotherapy has been widely explored for applications to both augment and suppress intrinsic host immunity. Clinical achievements have seen a number of immunotherapeutic drugs displace established strategies like chemotherapy in treating immune-associated diseases. However, single drug approaches modulating an individual arm of the immune system are often incompletely effective. Imperfect mechanistic understanding and heterogeneity within disease pathology have seen monotherapies inadequately equipped to mediate complete disease remission. Recent success in applications of combinatorial immunotherapy has suggested that targeting multiple biological pathways simultaneously may be critical in treating complex immune pathologies. Drug delivery approaches through engineered biomaterials offer the potential to augment desired immune responses while mitigating toxic side-effects by localizing immunotherapy. This review discusses recent advances in immunotherapy and highlights newly explored combinatorial drug delivery approaches. Furthermore, prospective future directions for immunomodulatory drug delivery to exploit are provided.

Engineering immunomodulatory biomaterials for type 1 diabetes

“…The use of multiple tolerogenic drugs is also an attractive idea for T1D immunotherapy 99 , because multiple drugs modulating different arms of the immune system can act synergistically and thus, more robustly mitigate disease than single agent treatments. However, multi-component approaches will require more complex regulatory, manufacturing, quality control, and assurance procedures than single-component drugs.…”

Nano and Microparticle Emerging Strategies for Treatment of Autoimmune Diseases: Multiple Sclerosis and Type 1 Diabetes

“…Building on this work, biomaterial platforms have been recently extended to immunomodulatory approaches. [ 60 ] Specifically, nano‐ and microparticles (NMPs) based therapies have shown promise in recent years in restoring homeostatic immunity. NMPs can encapsulate or have immunomodulatory factors conjugated to their surface and can be delivered in a diverse manner including systemically or locally.…”

“…Formulation of NMPs and the route of administration influence the effectiveness and the type of immunomodulation. [ 60–62 ] Intravenous and intraperitoneal injections provide better trafficking to the liver and spleen, [ 62,63 ] while subcutaneous injection may require the addition of recruitment factors, if the NMP system contains particles that are designed to be phagocytized, but are not small enough to drain passively. [ 64 ] With proper trafficking, subcutaneous delivery may be clinically favorable because of the ease and safety of administration compared to repeated bolus intravenous delivery.…”

“…In addition to administering antigen NMPs alone, combinatorial approaches have been used for T1D. [ 60 ] Some approaches have explored antigen delivery in combination with pro‐tolerogenic factors to modulate antigen‐specific immune tolerance. Co‐delivery of the Ahr ligand ITE and proinsulin via PEG‐coated gold NMPs showed efficiency in prophylactic treatment of 8‐week‐old NOD mice (Table 1).…”

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

“…[144–148] Disruption in the function, development or number of Tregs can lead to autoimmune and inflammatory diseases. [149,150] Moreover, it is now understood that an immunological balance of effector T cells and Tregs between the two populations is critical to maintain a healthy microenvironment. [149] Overall, Tregs are naturally tuned to regulate the proliferation of pathogenic effector T cells, and maintain immunological homeostasis in the ocular tissue.…”