Enhancing Bioavailability of Ultra‐High Concentration Antibody Formulations Using Ionic Liquids

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Abstract
Subcutaneous (SC) delivery of ultra‐high concentration antibody formulations (uHCAFs, > 150 mg/mL) is limited by excessive viscosity and poor bioavailability. Here, we present an ionic liquid made with choline and tryptophan (CHAT) as a multifunctional excipient that enables SC injection of antibody formulations at a concentration > 200 mg/mL by simultaneously reducing viscosity, enhancing tissue permeation, and stabilizing antibodies. Notably, CHAT‐formulated IgG exhibited viscosities below the injectability threshold (∼20 cP). In murine studies, SC delivery of CHAT‐formulated IgG achieved significantly greater systemic exposure than saline control, with up to a 2‐fold increase in area under the curve (AUC). Formulation of clinically relevant anti‐TNFα monoclonal antibody infliximab at >200 mg/mL with CHAT achieved near‐complete systemic exposure after SC administration, yielding an absolute bioavailability of ∼99% compared to ∼62% with saline. Mechanistically, CHAT disrupted collagen in the extracellular matrix, improving SC tissue penetration and accelerating antibody uptake (∼4× faster clearance from the injection site), and preserved antigen‐binding capacity after serum exposure (100% retention vs. ∼50% with saline). CHAT exhibited excellent biocompatibility with no histopathological or biochemical indications of toxicity in treated animals. Together, these results position CHAT as a single‐component platform for high‐dose, low‐volume SC delivery of monoclonal antibodies.
Funding Information
  • i2o Therapeutics

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