PEGylated DPPC/Anti-SNAP25 Antibody Targeted Liposomes: From Langmuir Monolayer Study to Formulations

Background: Molecule compatibility is an important factor to be considered before preparing antibody-targeted liposomes, stealth-liposomes, and stealth antibody-targeted liposomes. Objective: To determine the intermolecular interaction of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamide-N-[methoxy(polyethyleneglycol)-2000] (ammonium salt), DOPE PEG2000 and Anti-SNAP25 (AS25) in 1,2-dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) monolayer, and their liposomes. Methods: In this study, DPPC was used to create a monolayer mimicking the half membrane of liposomes to investigate its interactions with a polyclonal antibody, AS25, and DOPE PEG2000, respectively based on Langmuir-Blodgett (LB) techniques. The surface morphology of DPPC— AS25 and DPPC— DOPE PEG2000— AS25 bilayers were also imaged and analyzed by using atomic force microscopy (AFM) to support the LB findings. The LB findings were then utilized as a reference to prepare DPPC liposomes in this work. Results: The best mole ratio of DPPCDOPE PEG2000, determined to be 50 to 1, was used to study the interaction with the polyclonal antibody AS25. The free energy of mixing (〖Δ G〗_mix) of DPPC— DOPE PEG2000—AS25 was more negative than DPPC— AS25 in the entire investigated ranges, indicating that the ternary mixture of DPPC— DOPE PEG2000— AS25 was more compatible than the binary mixture of DPPC— AS25. The presence of DOPE PEG2000 in DPPC— AS25 increased the fluidity of the membrane, which resulted in a greater interaction of AS25 with DPPC. Conclusion: The constant values of particle size and zeta potential measurements of DPPC— DOPE PEG2000— AS25 liposomes showed agreement with the LB findings, indicating that LB is a good technique to predict precise liposomal formulations.