PH-responsive polyacrylic acid (PAA)-carboxymethyl cellulose (CMC) hydrogel incorporating halloysite nanotubes (HNT) for controlled curcumin delivery

Abstract

A pH-sensitive nanocomposite based on halloysite nanotubes (HNT) coated with polyacrylic acid (PAA)/carboxymethyl cellulose (CMC) hydrogel was synthesized for controlled delivery of curcumin (CUR) to MCF-7 cancer cells. Hazelnut oil was added to minimize the nanocomposite size and increase its uniformity via water/oil/water (W/O/W) double emulsion method. Likewise, Span 80 surfactant was incorporated to produce a nanoniosomal emulsion that increased the stability and retention of CUR as an anticancer drug. The molecular interactions between the nanocomposite components, its crystalline structure, surface morphology, size distribution and surface charge were analyzed through Fourier transformed infrared (FT-IR) spectroscopy, field emission-scanning electron microscope (FE-SEM), X-ray diffraction (XRD), dynamic light scattering (DLS) and zeta potential measurements, respectively. The resulting drug delivery system showed a 45% drug loading and an 87% encapsulation efficiency, which are amongst the highest values reported up to date for CUR nanocarriers. The zeta potential of the nanocomposite was about 36 mV, indicating good stability. A sustained drug release was observed, with 61% and 96% CUR released at pH 7.4 and 5.4 after 96 h, respectively, which confirms the pH-sensitivity of the developed nanocarrier. MTT assay demonstrated the strong toxicity of the nanocomposites against MCF-7 cancer cells. Also, 46% of cell death rate in the apoptotic phase was observed by flow cytometry. The results obtained herein support the great potential of PAA/CMC/HNT/CUR hydrogel nanocomposites as smart drug delivery vehicles for breast cancer treatment.