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.