Submicron-oleogel particles for enhanced oral delivery of hydrophobic compounds: In vitro and in vivo proof of concept

Oral administration is the preferred route for drug and bioactive delivery, although it raises great challenges due to the involvement of the gastrointestinal system and limited bioavailability. Herein, a novel submicron-oleogel particle system was developed using micro-structured edible oil to address the challenges associated with the low bioavailability of oral hydrophobic compounds. Oleogel particles were prepared using β-sitosterol and γ-oryzanol as oil structuring agents with dispersed dasatinib as a model drug. A particle size of approximately 160 nm and zeta-potential of around -25 mV were achieved along with a high drug entrapment efficiency of ∼90 %. <i>In vitro</i> analysis revealed greater stability of the submicron-oleogel particles during the gastric phase with minimal particle coalescence and significantly low dasatinib release. In the subsequent intestinal phase, the dasatinib bioaccessibility was enhanced through its integration into self-assembled mixed micelles formed during digestion. The presence of lipid byproducts and structuring agents played a crucial role in modulating this colloidal architecture and facilitating dasatinib solubilization, thereby improving its overall availability. An <i>in vivo</i> pharmacokinetic study confirmed enhanced dasatinib bioavailability in oil-containing formulations, attributed to improved micellization during digestion, which facilitated intestinal transport and overall absorption. Moreover, the submicron-oleogel particles displayed sustained release and absorption characteristics, attributed to the oleogel's mechanical durability. Overall, this study highlighted the enhanced therapeutic response while using oleogel particles, with a strong association between the <i>in vitro</i> and <i>in vivo</i> results. These findings underscore the potential of this novel carrier to advance the development of effective oral formulations for hydrophobic compounds.