Lipase-integrated gold-polysaccharide-protein hybrid nanocarrier for controlled and pH-sensitive ibuprofen delivery

In the present study, a novel hybrid nanocarrier integrating lipase into a polysaccharide-protein‑gold matrix (chitosan, casein, albumin, Au) was synthesized for the first time for the controlled release of the model drug ibuprofen (IBU). Lipase was used to facilitate interactions with a lipophilic model drug and to modulate its release via the carrier matrix. The findings of the study revealed that the nanocarrier exhibited high lipase immobilization efficiency (92%), significant drug loading efficiency (89.5%), and ∼ 14 nm primary nanoparticles observed by TEM, while FESEM showed larger aggregates of ∼63 nm. IBU release at 37 °C exceeded 82% between pH 1.2-9.5 and exhibited complex, pH-dependent kinetics: diffusion-dominated kinetics predominated at acidic pH, while release profiles at neutral and alkaline conditions were better represented by empirical and concentration-dependent models associated with changes in matrix properties. Swelling and moderate matrix degradation degree under physiologically relevant pH and alkaline conditions further facilitated accelerated and predictable release. The nanocarrier also demonstrated significant drug reloading capacity and enzymatic reusability. Overall, the findings suggest that lipase indirectly modulates drug release via the carrier matrix, while retaining 60-80% of its activity under physiologically relevant pH and alkaline conditions. In vitro cytotoxicity tests supported by IC₅₀ analysis indicated high cell viability, with IC₅₀ values of 317.2 μg/mL for carrier and 424.2 μg/mL for IBU-loading carrier. This hybrid system presents a novel strategy for modulating drug delivery behavior in pH-sensitive environments and provides a versatile framework for the development of multifunctional nanomaterials.