Injectable hydroethanolic physical gels based on Codonopsis pilosula polysaccharide for sustained anticancer drug delivery

The development of biocompatible carriers based on hydroethanolic physical gels for effectively encapsulating and delivering hydrophobic drug molecules is of particular interest. In this paper, we reported a novel hydroethanolic physical gel based on Codonopsis pilosula polysaccharide (CPP) prepared from the roots of C. pilosula. The gelation behaviors of the graded CPP fractions in a water-ethanol solvent system were evaluated, and the physicochemical and mechanical properties of the CPP-based gel (CPP-G) were characterized. The results indicated that CPP-G had consisted of a random physically crosslinked network formed by hydrophobic association of CPP chains and exhibited good mechanical strength, higher shear-thinning sensitivity and rapid, highly efficient self-recovering characteristics, ensuring superior performance in constructing injectable and self-recovering drug-loaded gels. Hydrophobic paclitaxel (PTX) and hydrophilic doxorubicin (DOX) were used as representative drugs to investigate the encapsulation and in vitro release behaviors of CPP-G, which exhibited long-term sustained release properties. Additionally, the evaluation of drug activity in drug-loaded gels further revealed the synergistic effect of CPP-G with the selected drugs on tumor inhibition against 4T1 and MCF-7 breast cancer cell lines. This work evaluated the feasibility of using the natural polysaccharide CPP to construct hydroethanolic physical gels and the applicability of the injectable drug-loaded gels for hydrophobic drug delivery.