Innovative oral formulations with silicon nanoparticles for co-delivery of poorly soluble drugs and hydrogen gas

Nanomedicine offers new opportunities for combination therapy by co-delivering multiple active pharmaceutical ingredients (APIs) for improved convenience and synergistic effects. Recently, hydrogen gas (H₂) has gained attention for its antioxidant effects suitable for treating a wide variety of conditions, including central nervous system disorders. Previous approaches have combined drugs and H₂ delivery via separate administrations. Porous silicon nanoparticles (Si NPs) offer a single platform for both drug delivery and H₂ generation through water reduction under mildly alkaline conditions. In this study, porous Si NPs synthesized by centrifugal chemical vapor deposition (cCVD) were loaded with the anti-epileptic drugs carbamazepine (CBZ) or phenobarbital (PB) to evaluate dual-delivery performance. Tablet and capsule formulations were developed, and H₂ and drug release was evaluated in buffers at pH 7.4-8.0. Although cCVD Si NPs previously demonstrated superior H₂ release, drug loading and formulation components reduced this capacity in a concentration-dependent manner. CBZ-loaded particles showed enhanced drug release but markedly lower H₂ output, unlike PB-loaded particles. Direct compression of tablets was challenging due to the low density and poor compressibility of the Si NP powder, and capsules filled with Si NP powder achieved higher H₂ release. Overall, dual delivery of drugs and H₂ using cCVD Si NPs is feasible, though formulation optimization remains an essential task for further development.