Biomimetic aminoated mesoporous silica xerogel exhibiting chiral surface topology for delivery insoluble drug with multiple-controlled manners and improved oral adsorption

Abstract

Driven by the clinical demand on improving the oral bioavailability and reducing the side effects of insoluble drug, aminoated mesoporous silica xerogel (named L/d-BPEIN-MSX) with chiral surface topology was constructed through a facile, economical, and biomimetic strategy within 2 min, and served as the carrier of indomethacin (IMC). In the synthetic process, L/d-tartaric acid (L/d-TA) self-assembled with branched polyethyleneimine (BPEI) to endow chirality and synergistic promoted silica deposition, while 3-aminopropyl triethoxysilane (APTES) polycondensated with the silica source to form aminoated mesostructure. By premixed strategy, IMC can be in situ loaded into L/d-BPEIN-MSX with high efficiency, which then became active in circular dichroism (CD) spectra owing to induced chirality. Noteworthy, IMC-L/d-BPEIN-MSX significantly improved the release rate of IMC with multiple controlled release manners. That is, d-BPEIN-MSX had favorable drug release behavior which could respond to the chiral stimuli, whereas l-BPEIN-MSX exhibited advantageous chiral surface topology that was beneficial for bio-processes related to oral adsorption. Undoubtedly, they increased the bioavailability of IMC to 8–9 times, displayed good anti-inflammatory effect, and reduced the gastrointestinal irritation of IMC. In addition, L/d-BPEIN-MSX had low toxicity and irritation, and was proven to be biodegradable and biocompatible, which could meet the requirement for biomedical applications.