A green approach for preparation of polyacrylic acid/starch incorporated with titanium dioxide nanocomposite as a biocompatible platform for curcumin delivery to breast cancer cells

Abstract

Curcumin (Cur) is a polyphenolic hydrophobic molecule with several biological uses, including cancer therapy. However, its widespread use in cancer treatment faces limitations due to its low solubility in acidic and neutral conditions, rapid removal from the circulatory system, and poor bioavailability. In order to overcome these challenges, a biocompatible and pH-sensitive carrier nanoplatform was designed for the specific delivery of curcumin to breast cancer cells. This nanocomposite containing polyacrylic acid (PAA), starch, and titanium dioxide (TiO2) was synthesized with a specific morphology through the water-in-oil-in-water green emulsification strategy. The nanocomposite structure was confirmed by Fourier transform infrared (FT-IR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, and field-emission scanning electrom microscopy (FE-SEM) imaging tests. The mean particle size of 151 nm for the PAA-Starch-TiO2 nanocomposite ensures specific entry into cancer cells and minimal damage to healthy cells. Loading efficiency (LE) and encapsulation efficiency (EE) for curcumin obtained 49.50 % and 87.25 %, which are desirable for a carrier nanoplatform. Compared to the physiological medium, the in-vitro release of curcumin was higher in the acidic conditions in all time intervals, which indicates the possibility of targeted drug release from the PAA-Starch-TiO2 nanocomposite around the tumor tissue. Furthermore, for better understanding of the release mechanism, the cumulative release data in both media were fitted with common mathematical kinetic models. Cytotoxicity tests against the MCF-7 cell line were performed using in vitro MTT and flow cytometry tests. The results showed that the PAA-Starch-TiO2 carrying Cur was more effective through increasing the bioavailability and controlled release of the drug compared to the free Cur. Also, the death of cancer cells in the presence of this nanocomposite compared to free Cur occurred mainly through the induction of apoptosis, which indicates the programmed death of cancer cells and the high efficiency of the designed nanocarrier.