Structural characterization of lipid-based colloidal dispersions using cryogenic transmission electron microscopy

Cryogenic transmission electron microscopy is an important technique for investigation of nano-structures formed by amphiphilic molecules in dilute aqueous solution. The basic principle and applicability of the method as well as sample preparation, interpretation of images and some artefacts are briefly outlined. The introductory section is followed by structural characterization of aqueous dispersions prepared from lipids with lamellar and non-lamellar propensities that form, respectively, liposomes and nano-size particles with a dense, frequently regular, internal structure. Eggphosphatidylcholine, soybean phosphatidylcholine, distearoyl phosphatidylcholine, dipalmitoyl phosphatidylcholine, and dioleoyl phosphatidylethanolamine are amongst the lipids with lamellar propensity, whereas glycerylmonooleate represents those of non-lamellar propensity. Steric stabilization of the nano-structures is achieved by using non-ionic block copolymers based on poly(ethylene glycol) that bear short blocks of lipid-mimetic units. Other physicochemical and biopharmaceutical techniques are employed to complement the structural investigations.