Powerful antioxidant -lipoic acid (LA) exhibits limited therapeutic efficiency due to
its pharmacokinetic properties. Therefore, the purpose of this work was to evaluate the ability of
silica-based composites of LA as well as its amide (lipoamide, LM), as new oral drug formulations, to
control their release and maintain their therapeutic concentration and antioxidant activity in the body
over a long time. The composites synthesized at different sol–gel synthesis pH and based on silica
matrixes with various surface chemistry were investigated. The release behavior of the composites in
media mimicking pH of digestive fluids (pH 1.6, 6.8, and 7.4) was revealed. The effects of chemical
structure of the antioxidants, synthesis pH, surface chemistry of the silica matrixes in the composites
as well as the pH of release medium on kinetic parameters of the drug release and mechanisms of the
process were discussed. The comparative analysis of the obtained data allowed the determination
of the most promising composites. Using these composites, modeling of the release process of the
antioxidants in accordance with transit conditions of the drugs in stomach, proximal, and distal parts
of small intestine and colon was carried out. The composites exhibited the release close to the zero
order kinetics and maintained the therapeutic concentration of the drugs and antioxidant effect in all
parts of the intestine for up to 24 h. The obtained results showed that encapsulation of LA and LM
