Sterilisation and preservation of vesicle formulations are important considerations for their viable manufacture for industry applications, particular those intended for medicinal use. Here, we undertake an initial investigation of the stability of hybrid lipid-block copolymer vesicles to common sterilisation and preservation processes, with particular interest in how the block copolymer component might tune vesicle stability.We investigate two sizes of polybutadiene-block-poly(ethylene oxide) polymers (PBd 12 -PEO 11 and PBd 22 -PEO 14 ) mixed with the phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) considering the encapsulation stability of a fluorescent cargo and the colloidal stability of vesicle size distributions. We find that autoclaving and lyophilisation cause complete loss of encapsulation stability under the conditions studied here. Filtering through 200 nm pores appears to be viable for sterilisation for all vesicle compositions with comparatively low release of encapsulated cargo, even for vesicle size distributions which extend beyond the 200 nm filter pore size. Freeze-thaw of vesicles also shows promise for the preservation of hybrid vesicles with high block copolymer content. We discuss the process stability of hybrid vesicles in terms of the complex mechanical interplay between bending resistance, stretching elasticity and lysis strain of these membranes and propose strategies for future work to further enhance the process stability of these vesicle formulations.Polymers 2020, 12, 914 2 of 17 liposomes can have inherent instabilities. Their membranes are highly flexible under bending deformations, but weak under stretching deformations, with a lysis strain of less than 5% [28,29]. The labile fluidity of the membrane can lead to transient membrane defects that frustrates long term encapsulation stability and lipid peroxidation can cause chemical instabilities in these structures.Polymersomes, due to their synthetic nature, are often less biocompatible than their lipid counterparts but offer greater mechanical stability and a broader chemical parameter space [30]. Amphiphilic copolymers that form vesicles can have several different architectures, the most common being AB diblock (A = hydrophilic, B = hydrophobic) [6], ABA [31] and ABC tri-block polymers [32] where A and C are chemically different hydrophilic blocks and finally graft copolymers [33]. Formation of polymersomes depends on the amphiphilic co-polymers molecular weight, polydispersity and hydrophilic/hydrophobic block lengths ratio, which is ideally less than 1:3 to form vesicular structures [34]. Their membranes are often thicker than liposome membranes, which provides greater bending resistance and their enhanced elasticity under stretching makes them tough and durable [22]. The polymer chemistry can be designed to minimise chemical instability but also to incorporate novel functionality. In blending liposomes and polymersomes to create hybrid vesicles, the ambition is to combine advantageous properties of these m...