Protection of Bevacizumab From Silicone Oil–Induced Inactivation by Liposomal Encapsulation

Purpose: Silicone oil endotamponades in retinal surgery induce aggregation and thus deactivate antibody drug formulations. Liposomes represent an approach to protect and deliver these drugs when administered intravitreally; however, their interactions with silicone oil endotamponades and their influence on encapsulated antibody agents have never been investigated. Methods: Bevacizumab was encapsulated in liposomes using dual centrifugation. Size, polydispersity index, zeta potential, and ultrastructure were characterized using dynamic light scattering, laser Doppler electrophoresis, and electron microscopy prior to and after incubation with Siluron 1000 and Densiron Xtra for up to 4 weeks. The behavior of liposomal bevacizumab was assessed using fluorescent ATTO 488 labeling. The size and circular dichroism of bevacizumab were measured after exposure to silicone oil and lysis of the liposomes. Results: Liposomal formulations of bevacizumab were stable upon silicone oil exposure for up to 4 weeks and showed no signs of lysis or migration. Encapsulated bevacizumab remained solely intraliposomal and did not diffuse through the lipid bilayer, as tracked by fluorescence measurements. The secondary structure of the antibody was preserved throughout the study, as demonstrated by circular dichroism. In contrast to non-formulated bevacizumab, liposomal bevacizumab showed no signs of aggregation after silicone oil exposure. Conclusions: The liposomal encapsulation of antibodies is an effective method to prevent their silicone oil-induced aggregation and inactivation. Liposomes are resistant to silicone oil exposure for a clinically relevant duration. Further in vivo studies should elucidate efficacy and release kinetics of liposomal encapsulated antibody drugs. Translational Relevance: This study unravels the potential of liposomes for application in silicone oil-filled eyes.