Molecular modeling of the PEGylated bilayer as a model for the PEGylated liposome surface in the bloodstream

The criteria for effectiveness of drug delivery liposomes (DDLs) are structural stability, site specific targeting, and lifetime in the bloodstream. Often to increase the lifetime in bloodstream DDL is coated with poly ethylene glycol (PEG). Although it helps to improve the lifetime, there exists plenty of room for improvement in bloodstream lifetime efficacy. The search for an alternative to PEG is a very active field of research, but to apply rational design to this, a knowledge of the mechanism through which PEG functions in a superior fashion to other superficially similar polymers must be determined, and currently our understanding of this is incomplete. We have used molecular dynamics simulation of a set of PEGylated membranes in varying conditions to gain insight into this. We have also performed MD simulation with the Cholesterol as a formulation component of DDL at its effect on stability of PEGylated DDL. Lastly we looked at the factors in the targeted delivery of the novel targeting moiety identified with phage display experiments. The moiety couldn't increase the efficacy of DDL when tested invitro and invivo. By MD we could identify the factors responsible for this by investigating surface structure of DDL.