Scalable fabrication of uniform nanoparticles for the efficient co-encapsulation of curcumin and procyanidins driven by multiple interactions

The co-delivery of curcumin (CUR) with other polyphenol bioactives often has synergistic benefits. However, conventional co-encapsulation carriers formed by precipitation frequently exhibit limited loading properties, particularly for bioactives with different solubilities. In this study, we designed a highly efficient vehicle for the co-delivery of hydrophobic CUR and hydrophilic procyanidins (PCs), adopting a multiple interactions–based strategy via a two-step flash nanoprecipitation (FNP) process. The optimal nanoparticles (NP), composed of a Fe II crosslinked PCs/CUR nanocore (NC) and a soy protein isolates (SPI) shell, showed high individual encapsulation efficiency (∼95%) and a total loading content of ∼38%. Compared with the conventional production process, FNP endowed our NP with a small size (133 nm) and good uniformity (polydispersity index = 0.267). Ultraviolet–visible and Fourier transform infrared spectra revealed multiple interactions (coordination and hydrogen bonding) among the carrier materials and bioactives, which played a central role in achieving excellent loading properties for both PCs and CUR. The core–shell structure of the NP greatly enhanced the thermal–light stability of the encapsulated PCs and CUR. Synergistic antioxidation effect was found between PCs and CUR, and the nano-formulation further increased the antioxidation efficiency. In vitro release experiments showed the favorable pH responsiveness of our NP in the vast gastrointestinal pH gradient effectively preventing the leakage of wrapped bioactives in the stomach pH environment, which benefits the intestinal delivery of the bioactives. Our nanoparticulate co-delivery system fabricated using the FNP process provides new insights into the formulation strategy of multiple bioactives and shows great potential for application in the fields of functional foods and dietary supplements.