Electrostatic interactions of monoclonal antibodies with subcutaneous tissue.

Aim: The majority of the subcutaneously injected monoclonal antibodies already on the market achieve 50–65% bioavailability, yet the fate of the portion that is lost remains unknown. This consistently incomplete systemic absorption affects the efficacy, safety and overall cost of the drug product. There are many potential factors that might influence the absorption, such as charge, hydrophobicity, formulation variables and the depth and volume of the injection. Materials & methods: To explore the possibility that the charge of the injected protein and/or formulation components is partially responsible for drug retention at the subcutaneous site, an ex vivo study, where the monoclonal antibodies were exposed to homogenized rat subcutaneous tissue, was performed. Results & conclusion: It was found that positively charged monoclonal antibodies bind to subcutaneous tissue in a manner that is dependent on ionic strength and pH, suggesting the electrostatic nature of the interaction. As expected, saturation of ...