title: Electrostatic interactions of monoclonal antibodies with subcutaneous tissue.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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 both nonspecific and electrostatic subcutaneous binding sites was observed after incubation with highly concentrated monoclonal antibody solutions. Additionally, it was demonstrated using model proteins that electrostatic effects of buffer components depend on ionic strength of ions bearing opposite charge rather than total ionic strength of the solution. These results suggest that electrostatic interactions may play a role in absorption processes of positively charged therapeutic proteins after subcutaneous administration.
authors: Merck Research Laboratories. 556 Morris Avenue, Summit, NJ 07901, USA.
authors: Henryk
authors: H
authors: Mach
authors: Sonia M
authors: SM
authors: Gregory
authors: Alexis
authors: A
authors: Mackiewicz
authors: Sarita
authors: S
authors: Mittal
authors: Anita
authors: A
authors: Lalloo
authors: Marc
authors: M
authors: Kirchmeier
authors: Mohammed
authors: M
authors: Shameem
mesh_terms: D000042:Absorption; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D055672:Static Electricity; D040521:Subcutaneous Tissue / Q000737:chemistry*
chemical_list: D061067:Antibodies, Monoclonal, Humanized