Nanoparticles provide long-term stability of bevacizumab preserving its antiangiogenic activity.

Unlabelled: Bevacizumab is one of the most common monoclonal antibodies used to treat cancer due to its antiangiogenic role. However, the frequent parenteral administrations are not attractive for the patient adhesion to the therapy. Nanoencapsulation of bevacizumab might be a useful alternative to increase administration intervals, due to controlled release properties. To achieve a long-term bevacizumab stability into PLGA nanoparticles, we developed an optimized and validated lyophilization protocol. The co-encapsulation of trehalose and bevacizumab into PLGA nanoparticles, associated to their lyophilization with external 10% (w/v) of trehalose, allowed maintenance of the physical-chemical characteristics of nanoparticles and bevacizumab secondary and tertiary structure. More relevant, the antiangiogenic activity of bevacizumab was kept over 6 months of storage while formulated with this protocol. No significant differences were found upon 6 months of storage at 4 °C and 25 °C/60% HR, and minor differences were observed for storage at 40 °C/75% HR, bringing to our knowledge, the first successfully report for monoclonal antibody storage at room temperature, without losing its structural and functional features. Our results served as starting point to understand the monoclonal antibody-based nanoparticle behavior over time, creating an innovative approach for a long-term monoclonal antibody stability.

Statement Of Significance: Nanoencapsulation of monoclonal antibodies has boost the interest of researchers as an alternative to the current antibody-based therapy, changing the route of administrations through controlled release of monoclonal antibodies. Despite good results have been achieved with nanoencapsulation process, no strategy has still found concerning a long-term stability of nanoparticles and monoclonal antibodies. In this study, the aim was to find out a validated and optimized method that allows a long-term stability of nanoparticles and antibodies. Over 6 months of storage, an optimized nanosystem was considered stable for both nanoparticles and antibody structure, at 4 °C and 25 °C, resulting the first successfully report for monoclonal antibody storage at room temperature.