Development of oleogel-based particles for oral delivery of hydrophobic drugs

Oral delivery is one of the most preferred routes, however orally delivery of hydrophobic is still a major challenge due to the limited oral bioavailability associated such molecules. To this end, structured oil-based particles, also termed oleogels, offer a very promising strategy overcoming this challenge. The inner microstructure of oleogel is made by the formation of a three-dimintional network, in which both an organic liquid solvent and other dispersed molecules can be entrapped. This combination of solid and liquid lipid components offers mechanical protection, on one hand, and micellization of the hydrophobic drug after digestion, on the other hand. The current research aims to improve the oral bioavailability of hydrophobic drugs by developing aqueous dispersion of oleogel-based particle formulations using β-sitosterol + γ-oryzanol mixture (PS) as oleogelator and Tween 80 as a surfactant. The effect of PS (5%, 10% and 15% w/w of the total lipid phase) and Tween 80 (1% and 3% w/w of total sample) concentrations on different characteristics such as droplet size, zeta potential, and morphology, of the colloidal dispersions were studied during 30 days storage. All PS oleogel-based particle dispersions exhibited similar behavior characterized by a bimodal distribution with a primary peak around 1 μm and a secondary peak around 0.030-0.040 μm which remained approximately the same over 30 days. The mean particle size values significantly decrease with the increase in PS and Tween 80 concentrations, indicating on a narrower particle size distribution. The high negative ζ-potential values (-30 to -50 mV) revealed the electrostatic stability mechanism of the colloidal dispersions. Drug-loaded PS oleogel-based particles were also prepared and their physical properties were examined in comparison to the native particles. The ability to mechanically and enzymatically breakdown the oleogel-particles was examined under simulated gastro-intestinal conditions with respect to drug loading and release. Overall, oleogel-based systems can open the path for the development of new drug delivery vehicles for a wide range of therapeutic agents able to overcome solubility and permeability challenges.