Lipidic spherulites: formulation optimisation by paired optical and cryoelectron microscopy

Abstract

Objective of this study was to assess the various steps leading to spherulite obtention by means of optical and cryoelectron microscopy. The formulation, resting and hydration steps were optimised. Green-based process and organic-based process were compared. It was found that spherulites could be obtained only when two key steps were followed: a prior resting phase of excipients and the shearing stress of the hydrated excipients. Moreover, the new formulation under study formed spherulites in the 100-200 nm range, which is smaller than previously reported spherulites. Such laboratory scale optimised process led the integration of spherulites in a larger number of prospective studies. Indeed, we finally showed that the encapsulated payload of a hydrophobic compound, such as the anti-angiogenic agent fisetin, was increased to a much higher degree than with a liposomal encapsulation.

Keywords: Fisetin; Lipidic assemblies; Multilamellar vesicles; Onion phase; Spherulite; cryoTEM.