Internalization and subcellular transport mechanisms of different curcumin loaded nanocarriers across Caco-2 cell model

Curcumin (Cur) and its nanomedicine were researched in Caco-2 cells to investigate the internalization and subcellular transport across Caco-2 cell monolayer membrane. Cur loaded polymer micelle (PM), nanoemulsion (NE) and liposome (Lipo) were prepared to explore the transport process incorporating endocytosis, intracellular trafficking and transcytosis in Caco-2 cells. Firstly, nanocarriers could contribute to the cellular uptake and improve the stability of Cur within the Caco-2 cells. The co-mediation of clathrin , lipid raft/caveolae and/or macropinocytosis were involved in the internalization of Cur nanopreparations, indicating the diversity and partial energy-dependency of the endocytosis. Secondly, the endocytosed nanocarriers with Cur successively transported from apical early endosome to late endosome with the extension of incubation time . Furthermore, the intracellular location of Cur nanomedicines in lysosome and endoplasmic reticulum (ER) were detected and illustrated the actual transport of Cur nanomedicine to lysosome and ER. Finally, nanocarriers could enhance the transcytosis of Cur, involving the energy-dependent patterns. Especially, Cur-PM exhibited more advantages in regulating and coordinating the entry and the exit of Cur. The study indicated that the coexistence of multiple transport pathways had the potency to promote nanocarriers transcytosis and provided a rational dosage design for oral Cur.