title: Effect of microencapsulation shear stress on the structural integrity and biological activity of a model monoclonal antibody, trastuzumab.
abstract: The aim of the present study was to investigate the influence of process shear stressors on the stability of a model monoclonal antibody, trastuzumab. Trastuzumab, at concentrations of 0.4-4.0 mg/mL, was subjected to sonication, freeze-thaw, lyophilisation, spray drying and was encapsulated into micro- and nanoparticles. The stressed samples were analysed for structural integrity by gel electrophoresis, SDS-PAGE, and size exclusion chromatography (SEC), while the conformational integrity was analysed by circular dichroism (CD). Biological activity of the stressed trastuzumab was investigated by measuring the inhibition of cell proliferation of HER-2 expressing cell lines. Results show that trastuzumab was resistant to the process shear stresses applied and to microencapsulation processes. At the lowest concentration of 0.4 mg/mL, a low percent ( 0.05). The results of this study conclude that trastuzumab may be resistant to various processing stresses. These findings have important implications with respect to pharmaceutical processing of monoclonal antibodies.
authors: School of Pharmacy, Royal College of Surgeons in Ireland, 123 St. Stephens Green, Dublin 2, Ireland. zramtoola@rcsi.ie.
authors: Ritesh M
authors: RM
authors: Pabari
authors: Benedict
authors: B
authors: Ryan
authors: Catherine
authors: C
authors: McCarthy
authors: Zebunnissa
authors: Z
authors: Ramtoola