Monoclonal antibodies (mAbs) are complex protein molecules, and their structural integrity impacts on their biological and pharmacological activity.
We investigated the effect of some stress factors, i.e., shaking, temperature, dilution, and light, on formulated anticancer monoclonal antibodies Nivolumab (Opdivo®) and Cemiplimab (Libtayo®) with or without dilution (saline and glucose solutions) trying to mimic their routine handling once released from the pharma industry, shipped to the hospital, diluted for the parenteral administration, and finally administered to the patients.
mAb stability analyses were run through biochemical and biophysical methodologies but a surface tensiometry analysis was added to get new information on the mAb chemico-physical changes induced by light. Indeed, a new concept of Integrated Analytical Approach was applied to the study of solid/liquid complex systems, determining the contact angle at the interface between the liquid samples and the perfluoropolyether liquid film as a “solid substrate”, without the influence of s/l interfacial friction forces and roughness surface.
Both mAbs showed to be quite stable under shaking and moderate temperature (37°C) for 45 days. However, they underwent chemico-physical modifications, mostly aggregation and amino acids oxidation, upon exposure to artificial sunlight. The light treatment produced major variations in surface tension of mAb+NaCl respect to mAb+glucose since aggregates influence surface tension properties. No significant effects to the secondary and tertiary structures were detected.
The dilution media commonly used for the administration to the patients, particularly the sterilized glucose solution containing degradation glucose products, i.e., HMF, showed a remarkable impact on the photostability of these drugs. Biological tests on the photomodified mAb gave information on the residual activity of the drug.
The instability of mAbs in sterile glucose solution upon light exposure could have a negative effect on the safety and efficacy of these very active anticancer drugs and should be considered in their real-life.