Protein-surface interaction phenomena have been studied
The interactions between therapeutic proteins and delivery deextensively during the past 15 years (1, 2). However, much vice surfaces may have a significant impact on the efficacy of a of this work has been focused on the adsorption of plasma recombinant protein-based biological therapy program. Proteinproteins such as fibrinogen, albumin, and g-globulin on the surface interactions may induce conformational changes and agsurfaces of implantable materials in efforts to assess hemogregation, resulting in the inactivation of the protein therapeutic compatibility (2-7). A notable exception is given by studies and even malfunction of the delivery device itself. Protein adsorpof the delivery of insulin. Formulated human insulin will tion phenomena may compromise the intended therapeutic benefit, aggregate on the surface of glass storage vials on standing drive up dosage levels, and increase treatment costs. We studied the interactions of formulated recombinant interleukin-2 (IL-2) (8); the aggregated protein is conformationally altered and is with silicone rubber tubing, a commonly used catheter material, inactive. Further, the major obstacle to the use of implantable in a recirculating system at 37ะC over a 24-h period. Bulk solution micropumps for the long-term delivery of insulin is the forprotein concentration and bioactivity assays were performed at mation of aggregates on pump surfaces, blocking flow chanintervals in order to quantify the impact of time of exposure of nels and valves (9). The adsorption of insulin appears to be the protein to the tubing. Attenuated total reflectance Fourier dependent on both the hydrophobicity/hydrophilicity of the transform infrared spectroscopy was used to monitor protein consurface and the aggregation state of the protein and may be formational changes upon adsorption as well as to quantify protein modulated by sugar-based nonionic surfactants (10-12).
deposition rates. Adsorption onto the tubing walls resulted in a 7
The insulin studies underscore the potential deleterious imto 20% reduction in the concentration of IL-2 after 24 h of exposure pact of therapeutic protein-device surface interactions. Rerelative to the initial concentration. At the same time, the residual IL-2 bioactivity levels decreased by 97 to 99.5% of initial activity cent studies have shown that formulated recombinant inlevels. These activity losses, which far exceed the adsorptive losses, terleukin-2 (IL-2) suffers tremendous bioactivity losses are a direct consequence of the protein-surface interactions. A upon continuous infusion (13). These losses were associated simple mathematical model was constructed in order to project with protein adherence to the tubing material of the infusion the impact of IL-2-surface interactions on treatment bioefficacy. device as well as the concentration-dependent precipitation