Cochleates : new insights into drug delivery system
In the past most of the investigations related to structural features or formation of cochleates have relied heavily on freeze fracture techniques. In this study, we have investigated cochleates of phosphatidylserines using different microscopy techniques for searching metastable intermediates and their coexistence with cochleates. Based on our morphological exploration, we speculate a probable order of well-defined hierarchical structures in the pathway for cochleate formation. The highlight of our study was the observation that, stack formation was an essential stage in the formation mechanism, as in its absence cochleate formation was hindered. Data from tomographic evaluation demonstrated cochleates to be cylindrically curved bilayers enclosing an inner channel. The dimensions of a cochleate vary statistically with changes in building lipids. We proposed a theoretical model based on these findings in order to predict dimensions of cochleates. We have developed a simple method for preparation of monodisperse cochleate formulations. We used a combined approach employing solvent effect along with controlled mixing by a microfluidic device. Lipid solution in an organic solvent was subjected to fast mixing with very small amount of aqueous solution of binding agent. The novel formulation obtained by this method consisted of microspheres made up of nanocochleates. We presumed that excess of ethanol reduced the bending energy and might have stabilized the interface of lipid stacks reducing the aggregation. The microspheres obtained were characterized using SAXS and electron microscopy and compared with cochleates obtained from preexisting methodologies. In conclusion this project has managed to capture new information regarding the structural details and formation mechanisms of cochleates. A simple, fast, efficient and highly reproducible method with strong control over process parameters was successfully developed for formation of monodispersed cochleate system.
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