Folate-Conjugated Chitosan-Pluronic P123 Nanogels: Synthesis and Characterizations towards Dual Drug Delivery

In this study, a self-assembled nanogel-based pluronic P123-grafted chitosan-folate (CP-FA) was fabricated as a paclitaxel/curcumin codelivery system. 1 H-NMR and TGA proved that the fabricating method of CP-FA was successful. Dynamic light scattering (DLS), zeta potentials, and transmission electron microscopy (TEM) exposed that CP-FA nanoparticles had a uniform size with a diameter of around <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mn>16.27</mml:mn><mml:mo>±</mml:mo><mml:mn>2.01</mml:mn></mml:math> nm in the colloidal solution and had better sustainable stability at a lower concentration than P123 due to the moderate positive potential value (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mn>39.43</mml:mn><mml:mo>±</mml:mo><mml:mn>3.45</mml:mn></mml:math> mV) and the lower critical micelle concentration (0.036 mg/ml). Dual drugs were loaded with CP-FA nanogels via self-assembly by the hydrophobic interaction between both hydrophobic therapeutic compounds (PTX and Cur) and the hydrophobic segment of the P123 copolymer. The high hydrophobicity of the segment induced a great loading efficacy of up to <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mn>98.63</mml:mn><mml:mo>±</mml:mo><mml:mn>0.42</mml:mn></mml:math> of PTX and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mn>97.82</mml:mn><mml:mo>±</mml:mo><mml:mn>0.48</mml:mn></mml:math> of Cur. In addition, the CP-FA nanogels exposed superior effects in a controlled release of these encapsulated therapeutic compounds for a long period of time. The anticancer activity of the dual-drug delivery system was evaluated using human breast cancer cell lines (MCF-7) via the IC50 value to compare with the PTX-loading CP-FA nanogel. The obtained results suggested that CP-FA/PTX-Cur displayed a remarkable improvement in anticancer activity at an IC50 value of <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mn>5.74</mml:mn><mml:mo>±</mml:mo><mml:mn>0.23</mml:mn></mml:math> nM which was higher than that of CP-FA/PTX (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mtext>IC</mml:mtext><mml:mn>50</mml:mn><mml:mo>=</mml:mo><mml:mn>8.20</mml:mn><mml:mo>±</mml:mo><mml:mn>1.41</mml:mn></mml:math> nM) due to the synergistic effect of both PTX and Cur. Thereby, a dual-drug delivery-system-based CP-FA of PTX and Cur has been proposed as a promising candidate in cancer therapy.