Physicochemical properties of lipid nanoparticles: Effect of lipid and surfactant composition

Abstract

Understanding the effect of lipid and surfactant composition on particle size and colloidal stability plays a pivotal role in designing lipid nanoparticles (LN) for drug delivery. With respect to our long-term goal, LN for brain delivery, formulations containing lipids and surfactants suitable for intravenous (i.v.) application were selected for the current formulation screening study. LN were prepared by hot high pressure homogenization (HPH) and were characterized during 1 year in terms of macroscopic appearance, particle size by photon correlation spectroscopy (PCS) and optical single particle sizing (OSPS), zeta potential (ZP), as well as physical state and polymorphism by differential scanning calorimetry (DSC). The LN dispersions showed a wide variability in macroscopic appearance, mean size and colloidal stability. Influence factors were the type and concentration of both, the lipid and surfactant component used. The most promising LN showed a small mean size (< 200 nm), a low polydispersity index (PI), (< 0.25) absence of particles in the several-micron range, and a slightly negative ZP (> −12 mV); DSC revealed that some represented supercooled liquids; such LN may be stable at room temperature for at least 1 year. The obtained results are regarded helpful for defining the design space for LN delivery systems, i.e., identifying possible designs and design parameters within the given HPH technology to be applied during future formulation development studies.

Keywords::

• Cutina (CP)
• Dynasan 114 (D14) and 116 (D16)
• Precirol ATO5 (POL5)
• witepsol E85 (WE85)
• polysorbates
• poloxamers
• photon correlation spectroscopy (PCS)
• optical single particle sizing (OSPS)
• differential scanning calorimetry (DSC)