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

Abstract

Abstract In this study, a biodegradable nanocomposite composed of polyhydroxybutyrate-co-chitosan and cobalt oxide (PHB-co-CS/Co 3 O 4 ) was developed for targeted and sustained in-vitro release of curcumin (CUR). The nanocomposite was prepared by varying the concentrations of Co 3 O 4 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. Co 3 O 4 NPs were synthesized by reacting cobalt acetate with sodium carbonate in ethylene glycol. CUR was first loaded onto the Co 3 O 4 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@Co 3 O 4 nanocomposite exhibited the strongest anticancer effect, with IC 50 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.