Functionalised mesoporous silica with stearic acid: A novel approach to improve octreotide delivery

• The complex showcased stearic acid needles and octreotide recrystallised compacts. • Octreotide permeability with complex (2.68%) higher than unloaded (0.8%). • Octreotide permeability with complex (2.68%) exceeded complex + SNAC (2.59%) and complex + SNAC + TPGS (1.81%). Oral peptide delivery remains challenging due to poor intestinal permeability and low bioavailability. Mesoporous silica have gained attention as drug carriers due to their high loading capacity and tuneable surface properties. This study investigates a stearic acid-functionalised mesoporous silica (SYLOID) complex for enhancing octreotide permeability. SEM imaging highlighted the presence of stearic acid needles on the silica surface, and localisation of octreotide was confirmed by 3D fluorescence imaging. Permeability studies using Caco-2 cells showed increased octreotide transport with the complex (2.68 ± 0.34%) compared to free octreotide (0.8 ± 0.16%). Transport with octreotide combined with permeation enhancers SNAC (2.59 ± 0.38%) or SNAC + TPGS (over 20%) was also measured, highlighting that conventional enhancers, particularly SNAC + octreotide, deliver substantially higher amounts than the complex alone. The observed permeability trend with the complex is attributed to stearic acid facilitating peptide association with the carrier and modulating interactions with intestinal cells. Apparent permeability (P app ) of octreotide was improved with the complex (5.77*10 −6 cm/s) compared to free octreotide (10 −6 cm/s). These results indicate that lipid-functionalised mesoporous silica can increase peptide permeability, though conventional permeation enhancers remain more effective in this model. Further studies, including in vivo validation, are warranted to assess the potential of the complex for oral peptide delivery.