Smart <scp>pH</scp>‐Sensitive Biopolymeric Nanocarrier Enables Controlled Release of Curcumin Through Biomimetic Biological Barriers

ABSTRACT Herein, the successful synthesis of a chitosan‐iron nanosphere‐based nanocarrier for smart delivery of curcumin (Cur) after penetration of the biomimetic barrier is reported. The synthesized nanocarrier displayed a spherical shape with an average size of 11 nm and a zeta potential value of −30.7 mV. The drug loading efficiency reached 64% ± 4% ( n = 3). Infrared analysis confirmed the functionalization of the nanocarrier with Cur. Thermogravimetric analysis (TGA) demonstrated the nanocarrier's stability. The biopolymeric nanospheres exhibited a PCZ at pH 8.22. pH‐responsive study indicated Cur satisfactory release (&gt; 80%) at pH = 7.4. Cur release kinetics followed a pseudo‐second order model ( R 2 = 0.933), indicating a controlled release behavior. In vitro permeation studies revealed that the polymeric nanocarrier successfully penetrated the biomimetic barrier and delivered Cur to the receptor compartment. Cytotoxicity studies using VERO cells and Artemia salina demonstrated that the nanocarrier exhibits low toxicity. Fluorescence microscopy images suggest that the nanocarrier has cytocompatibility with VERO cells, maintaining cell viability. However, hemolysis was observed at concentrations higher than 54 μmol L −1 in the hemolytic activity study. Finally, through albumin fluorescence suppression analysis, it was observed that the nanocarrier exhibited significant interaction with albumin, indicating its potential for transport through the circulatory system when administered intravenously.