# Curcumin delivery system based on biodegradable polyhydroxybuterate Chitosan copolymer and Cobalt oxide nanoparticles against colorectal cancer

## TL;DR

A biodegradable nanocomposite was developed to deliver curcumin for colorectal cancer treatment, showing effective drug release and anticancer activity.

## Contribution

A novel biodegradable nanocomposite using polyhydroxybutyrate-chitosan and cobalt oxide nanoparticles for curcumin delivery was developed and tested.

## Key findings

- The nanocomposite showed enhanced curcumin release in acidic tumor conditions.
- Lower molecular weight chitosan formulations released curcumin more rapidly.
- The PHB-co-LCS/10%CUR@Co3O4 system had an IC50 of 29.1 µg/mL against HCT-116 cancer cells.

## Abstract

In this study, a biodegradable nanocomposite composed of polyhydroxybutyrate-co-chitosan and cobalt oxide (PHB-co-CS/Co3O4) was developed for targeted and sustained in-vitro release of curcumin (CUR). The nanocomposite was prepared by varying the concentrations of Co3O4 nanoparticles (NPs) and using chitosan with different molecular weights (LCS, HCS) to optimize the release profile. The PHB-co-CS copolymer was synthesized through a coupling reaction between PHB-diol and the terminal isocyanate groups of chitosan, using stannous octanoate as a catalyst. PHB-diol was obtained via transesterification of PHB with ethylene glycol. Amine group in CS was protected by phthalic anhydrides followed by reaction with hexamethylene diisocyanato. Co3O4 NPs were synthesized by reacting cobalt acetate with sodium carbonate in ethylene glycol. CUR was first loaded onto the Co3O4 NPs and then dispersed within the PHB-co-CS copolymer matrix. Structural and chemical characterization was performed using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. In-vitro release studies were conducted in buffer solutions at pH 5.4 and 7.4, showing enhanced release in acidic conditions, which supports tumor-specific targeting. Formulations with lower molecular weight chitosan released curcumin more rapidly. Among the tested systems, the PHB-co-LCS/10%CUR@Co3O4 nanocomposite exhibited the strongest anticancer effect, with IC50 of 29.1 µg/mL against HCT-116 colorectal cancer cells. These results highlight the promise of combining green materials and sustainable approaches to develop effective, targeted drug delivery platforms for cancer treatment.

The online version contains supplementary material available at 10.1038/s41598-025-34587-y.