Effect of Microencapsulation Shear Stress on the Structural Integrity and Biological Activity of a Model Monoclonal Antibody, Trastuzumab
نویسندگان
چکیده
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.
منابع مشابه
Polyclonal Antibody against Different Extracellular Subdomains of HER2 Induces Tumor Growth Inhibition in vitro
Background: Human epidermal growth factor receptor 2 (HER2) has a crucial role in several malignancies. The extracellular domain of HER2 (HER2-ECD) has been extensively employed as an important target in passive and active immunotherapy. Isolated recombinant prokaryotic HER2-ECD subdomains were previously found to be ineffective in inducing anti-tumor antibody response. Objective: To employ rec...
متن کاملافقهای پزشکی فردی در درمان سرطان پستان : مقاله مروری
Breast cancer that is caused by the accumulation of genetic and epigenetic alterations, is one of the main causes of death resulted from cancer. Various therapeutic approaches have been introduced for this cancer and the traditional diagnosis and treatment is based on the prognosis estimation using cancer anatomic features (TNM system) and clinical results, but studies show different responses ...
متن کاملMeasurement of Affinity Constant of Anti-human IgG Monoclonal Antibodies by an ELISA-based Method
Background: The affinity of an antibody to its antigen is a crucial parameter in its biological activity and performance of an immunoassay such as ELISA. Affinity of most IgG specific MAbs are often determined by methods which require labeling of either antigen or antibody, and are sometimes difficult to control, do not always lead to the expected signal and often result in immunological modifi...
متن کاملInvestigation of the Bed and Structural Slopes on Bed Shear Stress and Flow Characteristics around an Impermeable Groyne
In this paper, effects of the cross shore and groyne wall slopes on flow parameters around an impermeable groyne were considered using a three-dimensional numerical CFD model (i.e., FLUENT). The k-ε turbulence model was used to evaluate the Reynolds stresses. The model was first applied to a vertical groyne on a flat bed and the model results were compared with the relevant experimental data. T...
متن کاملProduction and Quality Control of [67Ga]-DOTA-trastuzumab for Radioimmunoscintigraphy
Breast cancer radioimmunoscintigraphy targeting HER2/neu expression is a growing fieldof work in nuclear medicine research. In this study, trastuzumab was successively labeledwith [67Ga] GaCl3 after conjugation with DOTA-NHS-ester.The conjugates were purified by molecular filtration, the average number ofDOTA conjugated per mAb was calculated and total concentration was determined byspectrophot...
متن کامل