Naproxen-loaded mesoporous silica nanoparticles: How can the process of incorporation affect drug placement, drug release and the in vitro naproxen irritant potential?

Abstract

Mesoporous silica nanoparticles (MSN) serve as versatile drug nanocarriers to avoid the interaction of highly irritant drugs with stomach mucosa, such as nonsteroidal anti-inflammatory drugs (NSAIDs). In this study, spherical and nanometric particles (181 ± 11 nm) with long-channel nanopores (∼2.5 nm in diameter) hexagonally arranged were synthesised. The NSAID naproxen (NPX) was incorporated into MSN by using the incipient wetness method. NPX ethanolic solutions of 30 mg mL⁻¹ (NPX-ES-30) and 40 mg mL⁻¹ (NPX-ES-40) were employed to obtain MSN-NPX30-1 and MSN-NPX40-1, corresponding to 8.26 % and 10.12 % (w/w) NPX loading, respectively. A second incorporation was performed to produced MSN-NPX30-2 and MSN-NPX40-2, with 13.45 % and 16.78 % (w/w) NPX loading, respectively. A reduction in surface area and pore volume was observed for all drug-loaded formulations compared to bare MSN. Notably, formulations prepared with NPX-ES-40 exhibited a less pronounced reduction, indicating that a portion of the drug was likely positioned outside the MSN pores. In contrast, NPX-ES-30 formulations showed efficient internalization of NPX into the mesopores, resulting in a more significant reduction in surface area and pore volume following drug incorporation. The enhanced silica–drug interaction in these formulations resulted in a slower NPX release rate compared with the NPX-ES-40 formulations, and a lower in vitro irritation score for the hen's eggs test on chorioallantoic membrane. In conclusion, the concentration of the NPX solution influenced the drug placement within MSN pores and, therefore, the NPX drug release rate and in vitro irritant potential.